– Gjellan, Kirsti, et al. 2012

A collaborative in vitro dissolution study was performed comparing the Flow-through cell (FTC) method with the USP Paddle method. The objective was to compare the two methods regarding their suitability for changing the pH of a dissolution medium and for measuring the in vitro dissolution of a gastro-resistant dosage form. Aspirin, a gastro-irritant substance in an enteric-coated, multiple-unit dosage form, was used as the test material. The results show that the FTC method gives comparable results compared with the Paddle method. The FTC method is also more convenient to use for shifting the pH from an acidic condition at pH 1.2 to a pH of 6.8. The effect of different ionic strengths of the dissolution media on dissolution rate results was observed for the test product by using the FTC method.

– Komarova, D.S., Demkin, K.M., Mochalova, M.S. et al.. January 2024

In the present article chitosan-based aerogel particles with the impregnated lidocaine hydrochloride via supercritical adsorption method were studied. During the research particles of 1% chitosan aerogel were obtained by the dripping method. Drying of the obtained gels was carried out in a supercritical fluid. The impregnation of lidocaine hydrochloride into the pores of the chitosan-based aerogel was carried out by supercritical adsorption with varying process temperature. The article presents the schemes of apparatuses for the drying process and supercritical adsorption. Using the method of high-performance liquid chromatography, the amount of impregnated drug in the obtained aerogel samples was determined. The sorption capacity of the obtained particles was determined using a solution simulating blood, Earle’s Balanced Salt Solution. It was found that the samples have a sorption capacity comparable to the sorption capacity of aerogel particles without impregnated lidocaine hydrochloride. Using X-ray phase analysis, the state of the drug in the pores of the chitosan-based aerogel was investigated. In the course of the research work a release kinetics of lidocaine hydrochloride from aerogel particles was also obtained using a dissolution tester Sotax AT 7 Smart, the “rotating paddle” method. The results of the conducted analytical studies demonstrate that when an active pharmaceutical ingredients is impregnated into aerogel particles by supercritical adsorption, it is possible to obtain a local hemostatic agent with a therapeutic anesthetic effect and a controlled dosage of the active pharmaceutical substance to relieve pain when used.

– Cespi, Marco, et al. January 2014

Introduction Despite the fact that sustained administration of hormones has been shown to be effective in aquaculture, at the present time, only minimal research is devoted to this issue and only a few sustained release systems have been developed and tested on fish breeding, such as cholesterol pellets implants, biodegradable microspheres, non-degradable monolithic implants and more recently, osmotic pumps. Although these systems have generally demonstrated a good performance when administrated to fish, the production and wider distribution on an industrial scale appears improbable due to the high production cost and to the difficult administration. The use of a parenteral thermogelling systems has previously been shown to be effective for controlled release of hormones when applied in different animal species. These formulations increased the relative bioavailability of steroidal hormones and resulted in the sustained release of testosterone after a single subcutaneous (s.c.) injection in rabbits. Aim of the work The purpose of this study was to develop and evaluate a delivery system comprising a thermosensitive gel for the sustained release of 17β-estradiol (E2) in fish, over an extended period of time after a single intramuscular (i.m.) injection and for the improved reproductive performance in fish. Experimentals Poloxamer 407 (LUTROL F-127) was used to formulate the thermo-sensitive gelling system. Rheological analysis was performed using (Stress-Tech, Reologica Instruments, Lund, Sweden) equipped with a cone-plate geometry (4/40). In vitro release of E2 was evaluated using an USP dissolution apparatus 2 (AT7 smart, Sotax, CH) equipped with teflon Enhancer Cells (Agilent, USA). In vivo studies have been performed on goldfish (Carassius auratus), analyzing the plasma concentration of both E2 and vitellogenin (VGT) with Enzyme-immunoassay (EIA) and ELISA techniques. Results and discussion The poloxamer 407 based formulation exhibited a gel point at 20°C and behaved as a Newtonian low viscosity system at temperature lower than 15°C. The results demonstrate that a single i.m. injection of the thermogel formulation containing E2 can increase relative bioavailability of the hormone resulting in prolonged presence of high plasma VTG levels. E2 and VTG levels after i.m. injection of gel-E2 remained high for more days compared to the duration observed following both oil-E2 (this study) and double E2 injection experiments. Overall, the observed levels are comparable to those of mature vitellogenic female goldfish. Conclusion This work demonstrates that the poloxamer 407 thermogelling system show the potential to work as a long-acting sustained release vehicle for steroidal hormones in fish. The fast preparation, the low cost of the main formulation components, the high versatility, together with the much easier administration compared to other prolonged release systems currently studied such as implants, make these systems particularly promising in the field of hormonal treatment in aquaculture.

– Curran, David, et al, 2024

Commercially available dissolution vessels used with United States Pharmacopeia (USP) apparatus 1 and 2 typically have nominal inner diameters of 100 or 104 mm. Little data are available in the literature to evaluate whether equivalent dissolution results are obtained when the same product is tested in both types of vessels. This study provides some additional data. Three immediate-release tablet products and a suspension product were tested in the two vessel types, across a range of paddle speeds. Superimposable dissolution profiles were obtained for all experiments. These data, although not exhaustive, suggest that these two vessel diameters may be considered equivalent from a hydrodynamic perspective, and thus, represent a low risk for method transfers between instruments that use vessels with 100-mm and 104-mm inner diameters.

– Mann, James, et al. November 2022

Commercially available dissolution vessels used with United States Pharmacopeia (USP) apparatus 1 and 2 typically have nominal inner diameters of 100 or 104 mm. Little data are available in the literature to evaluate whether equivalent dissolution results are obtained when the same product is tested in both types of vessels. This study provides some additional data. Three immediate-release tablet products and a suspension product were tested in the two vessel types, across a range of paddle speeds. Superimposable dissolution profiles were obtained for all experiments. These data, although not exhaustive, suggest that these two vessel diameters may be considered equivalent from a hydrodynamic perspective, and thus, represent a low risk for method transfers between instruments that use vessels with 100-mm and 104-mm inner diameters.

– Baxter, Jennifer L., Joseph Kukura, and Fernando J. Muzzio. November 2005

The USP tablet dissolution test is an analytical tool used for the verification of drug release processes and formulation selection within the pharmaceutical industry. Given the strong impact of this test, it is surprising that operating conditions and testing devices have been selected empirically. In fact, the flow phenomena in the USP test have received little attention in the past. An examination of the hydrodynamics in the USP apparatus II shows that the device is highly vulnerable to mixing problems that can affect testing performance and consistency. Experimental and computational techniques reveal that the flow field within the device is not uniform, and dissolution results can vary dramatically with the position of the tablet within the vessel. Specifically, computations predict sharp variations in the shear along the bottom of the vessel where the tablet is most likely to settle. Experiments in which the tablet location was carefully controlled reveal that the variation of shear within the testing device can affect the measured dissolution rate.

– Webster, Gregory K., et al. November 2020

Cleaning in any Good Manufacturing Practice (GMP) laboratory is an important aspect of the analytical experiment. The laboratory must ensure the equipment does not contain residual active pharmaceutical ingredients (APIs) or impurities that may affect the outcome of any current or future experiments. While this is standard practice for GMP manufacturing operations, common laboratory equipment is often held to less stringent standards. The potential manhours lost due to investigations for extraneous peaks and contamination can be significant and cause delays in releasing product. Potential compliance issues related to ineffective cleaning are particularly important for dissolution instrumentation. Our laboratory has modeled the challenges of cleaning automated dissolution systems using representative soluble and poorly soluble APIs. Poorly soluble drugs often entail the use of surfactants in the dissolution media which also have a potential carryover issue. Using a manufacturing cleaning validation based approach, the study discussion presented will address the cleaning effectiveness for both sample and media considerations.

– Mekjaruskul C et al. June 2024

The present study systematically investigates the impact of active pharmaceutical ingredient (API) variables and oleaginous base characteristics on the in vitro release (IVR) performance of ophthalmic ointments, utilizing dexamethasone as a model drug. The interplay between selected attributes (i.e., particle size distribution, crystallinity, and polymorphic form for API, and rheological factors for compendial-grade white petrolatum) and IVR performance was investigated. APIs from different vendors exhibited variations in crystallinity and polymorphism. Ointments containing amorphous dexamethasone presented higher release amounts/rates compared to crystalline counterparts, emphasizing the role of physical state in release kinetics. Variations in particle size of this lipophilic API (5.4 - 21.2 µm) did not appear to impact IVR performance significantly. In contrast, white petrolatum's rheological attributes, which varied substantially within USP-grade petrolatum, were found to critically affect the drug release rate and extent of the ointment. The study's comprehensive analysis establishes a coherent connection between the quality attributes of both API and petrolatum and IVR, delineating their intricate interdependent effects on ophthalmic ointment performance. These findings provide reference to formulation design, quality control, and regulatory considerations within the pharmaceutical industry, fostering a robust foundational understanding of commonly overlooked quality attributes in ophthalmic ointments.

– Quanying Bao et al. April 2017

It is essential as well as challenging to develop a reliable in vitro release testing method for determining whether differences in release profiles exist between qualitatively and quantitatively equivalent ophthalmic ointment formulations. There is a lack of regulatory guidance on in vitro release testing methods for ophthalmic formulations. Three different in vitro release testing methods 1) USP apparatus 4 with semisolid adapters; 2) USP apparatus 2 with enhancer cells; and 3) Franz diffusion cells were investigated. Qualitatively and quantitatively equivalent ointments were prepared via hot melting and simple mixing methods using four different sources of excipients (i.e. white petrolatum). The ointment formulations were charac-terized for content uniformity, particle size, and rheological parameters. All the formulations showed adequate content uniformity and similar particle size. The ointments prepared via the hot melting processes showed higher rheological parameters, as did the ointments prepared using ‘white’ petrolatum that exhibited a yellowish color. The three in vitro release testing methods were compared and evaluated for reproducibility, discriminatory capability, and correlation with the rheological parameters. Compared with the compendial methods, the non-compendial method (Franz diffusion cells) showed poorer reproducibility. All three methods possessed the ability to discriminate between the ophthalmic ointments with manufacturing differences. However, the USP apparatus 4 method displayed the largest margin of discrimination between the release profiles of the different ophthalmic ointments. In addition, the in vitro release rate obtained using the USP apparatus 4 method showed the strongest logarithmic linear correlation with the rheological parameters (Power law consistency index (K value) and crossover modulus) compared to the other two methods.

– Mekjaruskul C, et al. December. 2025

This investigation compares in vitro release, ex vivo release and permeation, and in vivo ocular pharmacokinetics to render biologically informed evaluations of ophthalmic semi-solid drug products containing dexamethasone (hydrophobic) and tobramycin (hydrophilic). Both drugs were formulated with three petrolatum matrices (IGI® 320 A, IGI® 386, or Spectrum®) with distinct rheological character and benchmarked against the reference listed drug, Tobradex®. Temperature-sweep rheology revealed that IGI® 386 most closely reproduced the viscoelastic profile of the reference product. USP Apparatus I release testing with surfactant-free medium provided maximal discrimination for dexamethasone (Tobradex® > IGI® 320 A > IGI® 386 > Spectrum®), and rank-order release rates correlated strongly with ex vivo corneal permeation and in vivo corneal exposure. In contrast, tobramycin required a polysorbate-containing medium to resolve formulation differences in vitro, yet those differences did not persist ex vivo or in vivo, consistent with its rapid dissolution and diffusion, which attenuate matrix effects. The data demonstrate that drug solubility dictates the choice of biorelevant release conditions in petrolatum-based ophthalmic ointments: surfactant-free media capture formulation-dependent release for hydrophobic actives, whereas hydrophilic actives may yield artifactual discrimination when surfactant is present. However, formulations indistinguishable in vitro were typically similar in their in vivo ocular pharmacokinetics. By integrating tiered models, the framework enhances understanding of critical quality attributes, supports regulatory decision-making, and may help reduce reliance on animal studies, thereby expediting the development of therapeutically equivalent generic ophthalmic ointments.

– Adrover, Alessandra, et al. May 2015

Thin strips of polymeric films have been recently proposed as a promising drug delivery alternative for non-compliant patients (geriatric, children, bedridden) and different therapeutic classes (e.g. vaccines, peptides and nanoparticles). In this work, a new millifluidic continuous flow-through device is proposed for dissolution studies of oral dissolving strips. The millifluidic device is covered by patent. The flow-through device mimics mouth physiological conditions thanks to the laminar tangential solvent flow, flow rates order of 1 mL/min and low hold-up volume (1 cm3). Pilot dissolution tests have been performed on commercially available melatonin strips with different initial drug loadings and thicknesses. Dissolution profiles obtained with the flow-through device are compared with those obtained using the official USP XXXVII basket (USP 1) and paddle (USP 2) apparatuses.

– Fandiño, Octavio E., et al. 2021

Background: Nitazoxanide (NTZ) is a broad spectrum antimicrobial agent with poor aqueous solubility and low bioavailability. Thus, the generation of new solid forms of NTZ is relevant to improve its unfavorable properties. The present study deals with the application of mechanochemistry for the preparation of alternate solid forms of NTZ, using saccharine (SAC) as coformer.

Methods: NTZ-SAC mixtures were prepared by neat and liquid-assisted grinding (LAG) and characterized using differential scanning calorimetry (DSC), hot stage microscopy (HSM), X-ray Powder Diffraction (XRPD), 13C Solid-state Nuclear Magnetic Resonance (SSNMR) and Diffuse Reflectance Infrared Fourier Transform (DRIFT) spectroscopy. Powder dissolution (PD) profiles were obtained with USP apparatus 2 in buffer phosphate pH 6.5 with 0.25% TweenÒ 80-0.25% triethanolamine and in 0.25% sodium lauryl sulfate, at 37 ºC±0.5 ºC and 75 rpm. Drug release was characterized in terms of dissolution efficiency (DE).

Results: XRPD, SSNMR and DRIFT indicated that NTZ and SAC did not cocrystallize but DSC and HSM revealed that they formed a binary eutectic mixture which melted near 176 C, a melting temperature lower than those of NTZ and SAC. PD data indicated that the 1: 1 NTZSAC sample obtained by LAG exhibited a slightly higher DE than pure NTZ in the two assayed media.

Conclusion: NTZ and SAC formed a eutectic, the first reported for this drug, which improved its dissolution rate and opened the pathway for studies searching for new eutectics with better biopharmaceutical attributes than NTZ and the NTZ-SAC eutectic reported herein.

– Kelleher, J. F., et al. 2018

The purpose of this work was to investigate the application of different advanced continuous processing techniques (hot melt extrusion and spray drying) to the production of fixed-dose combination (FDC) monolithic systems comprising of hydrochlorothiazide and ramipril for the treatment of hypertension. Identical FDC formulations were manufactured by the two different methods and were characterised using powder X-ray diffraction (PXRD) and modulated differential scanning calorimetry (mDSC). Drug dissolution rates were investigated using a Wood’s apparatus, while physical stability was assessed on storage under controlled temperature and humidity conditions. Interestingly both drugs were transformed into their amorphous forms when spray dried, however, hydrochlorothiazide was determined, by PXRD, to be partially crystalline when hot melt extruded with either polymer carrier (Kollidon® VA 64 or Soluplus®). Hot melt extrusion was found to result in significant degradation of ramipril, however, this could be mitigated by the inclusion of the plasticizer, polyethylene glycol 3350, in the formulation and appropriate adjustment of processing temperature. The results of intrinsic dissolution rate studies showed that hot-melt extruded samples were found to release both drugs faster than identical formulations produced via spray drying. However, the differences were attributable to the surface roughness of the compressed discs in the Wood’s apparatus, rather than solid state differences between samples. After a 60-day stability study spray dried samples exhibited a greater physical stability than the equivalent hot melt extruded samples.

– Thiry, Justine, et al. June 2016

The difficulty to find a relevant in vitro dissolution test to evaluate poorly soluble drugs is a well-known issue. One way to enhance their aqueous solubility is to formulate them as amorphous solid dispersions. In this study, three formulations containing itraconazole (ITZ), a model drug, were tested in seven different conditions (different USP apparatuses and different media). Two of the formulations were amorphous solid dispersions namely Sporanox®, the marketed product, and extrudates composed of Soluplus® and ITZ produced by hot melt extrusion; and the last one was pure crystalline ITZ capsules. After each test, a ranking of the formulations was established. Surprisingly, the two amorphous solid dispersions exhibited very different behavior depending primarily on the dissolution media. Indeed, the extrudates showed a better release profile than Sporanox® in non-sink and in biphasic conditions, whilst Sporanox® showed a higher release profile than the extrudates in sink and fasted simulated gastric conditions. The disintegration, dynamic light scattering and nuclear magnetic resonance results highlighted the presence of interaction between the surfactants and Soluplus®, which slowed down the erosion of the polymer matrix. Indeed, the negative charge of sodium dodecyl sulfate (SDS) and bile salts interacted with the surface of the extrudates that formed a barrier through which the water hardly diffused. Moreover, Soluplus® and SDS formed mixed micelles in solution in which ITZ interacts with SDS, but no longer with Soluplus®. Regarding the biphasic dissolution test, the interactions between the octanol dissolved in the aqueous media disrupted the polymer — ITZ system leading to a reduced release of ITZ from Sporanox®, whilst it had no influence on the extrudates. All together these results pointed out the difficulty of finding a suitable in vitro dissolution test due to interactions between the excipients that complicates the prediction of the behavior of these solid dispersions in vivo.

– Školáková, T.; Slámová, M.; Školáková, A.; Kadeřábková, A.; Patera, J.; Zámostný, P. June 2019

The aims of this study were to investigate how the release of tadalafil is influenced by two grades of poly-vinylpyrrolidone (Kollidon® 12 PF and Kollidon® VA 64) and various methods of preparing solid dispersions (solvent evaporation, spray drying and hot-melt extrusion). Tadalafil is poorly water-soluble and its high melting point makes it very sensitive to the solid dispersion preparation method. Therefore, the objectives were to make a comparative evaluation among different solid dispersions and to assess the effect of the physicochemical nature of solid dispersions on the drug release profile with respect to the erosion-diffusion mechanism. The solid dispersions were evaluated for dissolution profiles, XRD, SEM, FT-IR, DSC, and solubility or stability studies. It was found that tadalafil release was influenced by polymer mo-lecular weight. Therefore, solid dispersions containing Kollidon® 12 PF showed a faster dissolution rate compared to Kollidon® VA 64. Tadalafil was released from solid dispersions containing Kollidon® 12 PF be-cause of the combination of erosion and diffusion mechanisms. The diffusion mechanisms were predominant in the initial phase of the experiment and the slow erosion was dissolution-controlling at the second stage of the dissolution. On the contrary, the tadalafil release rate from solid dispersions containing Kollidon® VA 64 was controlled solely by the erosion mechanism.

– Gjellan K, Graffner C 1989

The applicabilities of the Paddle, the Basket and the Flow-Through methods have been investigated for seven different rectal compositions of hydrophilic and lipophilic type. The formulations were studied with respect to in vitro dissolution rate and behaviour in the different techniques. It was found that the composition has a considerable influence on the behaviour of the dosage form and this must be taken into account when judging the applicabilities of the three dissolution tests. The Paddle, the Basket and the Flow-Through methods are considered to be equivalent methods for the dissolving suppositories tested. The Flow-Through method is applicable for all the seven compositions tested; however, a low flow rate (8 ml/min) is necessary to use for soft gelatin capsules when both the coefficient of variation and the behaviour of the dosages within the techniques is taken into consideration.

– Ilana Gonzales-Hernadez, et al. May 2025

Studying the dissolution profile is a suitable method for the comparison of novel or special dosage forms, including oral and parenteral suspensions, soft gel capsules, and transdermal patches. Mebendazole is a broad-spectrum benzimidazole approved by United States Food and Drug Administration to treat different parasitic diseases. Despite its wide use, there is no compendial dissolution requirement for oral suspensions. The objective of this study was to develop a discriminatory in vitro release test for mebendazole suspensions. Methods: United States Pharmacopeia (USP) apparatus 2 (paddle) and 4 (flow-through cell) were selected, and 0.1 N hydrochloric acid with 1% sodium lauryl sulfate was used as the dissolution medium. In apparatus 2, a 50-rpm agitation rate and sample insertion mode in the dissolution vessel were evaluated. In apparatus 4, flow rate, bed size, and open and closed configurations were assessed. Dissolution profiles of three commercial products were analyzed. Results: Dissolution studies using USP apparatus 2 showed that all products complied with very rapid dissolution criteria, and the method was not able to discriminate between products. For apparatus 4, a flow rate of 16 mL/min was selected. No differences in dissolution behavior for the reference product were found between open and closed-loop configuration. Statistical differences in dissolution profiles were found among products using the open-loop configuration. Conclusion: USP apparatus 4 with the open-loop configuration had more discriminatory power than apparatus 2 in assessing the dissolution release from oral mebendazole suspension products. The developed method could be suitable for quality control and dissolution profile comparison of mebendazole commercial formulations.

– Medina, Jose Raul, Mariel Cortes, and Erik Romo June 2017

Objective: The aim of this study was the comparison of the in vitro release performance of ibuprofen generic suspensions and reference, based on the hydrodynamic environment generated by the flow-through cell method (USP Apparatus 4). Results were compared with those obtained by the use of the USP Apparatus 2.

Methods: The Advil® suspension (2 g/100 ml) and two generic formulations with the same dose were tested. Dissolution studies were carried out using a USP Apparatus 4 Sotax CE6 with 22.6 mm cells, laminar flow at 16 ml/min, and pH 7.2 phosphate buffer at 37.0±0.5 °C as dissolution medium. Ibuprofen was quantified spectrophotometrically at 222 nm. The in vitro release of the three drug products were studied using the USP Apparatus 2. The dissolution profiles of generic products were compared with the reference by model-independent, model-dependent, and analysis of variance (ANOVA)-based comparisons.

Results: The dissolution profile of the generic product A was similar to the dissolution profile of reference, only with the use of the USP Apparatus 4. The f₂ similarity factor was>50 and no significant differences were found with dissolution efficiency data (*P>0.05). Similar results were found with the comparison of t_50% and t_63.2% values. Similar dissolution profiles between generic product A and reference were also found with ANOVA-based comparisons.

Conclusion: The flow-through cell method was adequate for study the in vitro release of ibuprofen suspensions. It is necessary to evaluate the in vivo performance of the drug products used in order to estimate the predictability of the proposed methodology.

– C. Parulski, E. Gresse, O. Jennotte, A. Lechanteur, and B. Evrard, March 2022

INTRODUCTION In recent years, the use of three-dimensional (3D) printing for drug manufacturing has considerably increased in the pharmaceutical field. The modification of the drug release profile by the elaboration of complex geometries is a reason why 3D printing and, more specifically, Fused Deposition Modeling (FDM) appears as a promising tool. Nowadays, many active pharmaceutical ingredients (API) are classified in the Biopharmaceutics Classification System class II (BCS II) since they are poorly soluble. Elaboration of new solid oral forms by HME and FDM can be a solution to increase the dissolution rate of these BCSII API by the amorphisation of the drugs and the modification of the geometry of the printed forms. Therefore, the goal of this work is to enhance the solubility and the dissolution rate of poorly solu-ble drugs by the use of hot-melt extrusion (HME) coupled with 3D printing. MATERIALS AND METHODS Materials: Itraconazole (ITZ), a BCS II API, was chosen as the model drug. Four formulations containing 25% of ITZ and different proportions of Affinisol® 15LV (hydroxypropylmethylcellulose) and Kollidon® VA 64 (vinylpyrrolidone-vinyl acetate copolymer) were elaborated thanks to previous studies. Methods: - HME and FDM 3D Printing : HME process (Pharma 11, ThermoFisher Scientific®, Waltham, MA, USA) was performed on the four formulations to produce three batches of filaments. For each formulation except formulation 4, which was not printable, printed forms with infill densities of 20%, 50% and 80% and thickness of 5.8 mm, 4.4 mm and 3.4 mm, respectively, were printed (Prusa® i3MK3 3D printer, Prusa Research, Pra-gue, Czech Republic). Tablet thickness were modified to keep a constant drug load of 100 mg in each form since a comparison is made with Sporanox®, the correspondent commercialized drug in Belgium. - Differential Scanning Calorimetry (DSC): Printed forms were analyzed in triplicates by DSC (Mettler- Toledo, Schwerzenbach, Suisse) every four weeks to determine the physical state of ITZ. - High Performance Liquid Chromatography (HPLC): The amount of ITZ in filaments and printed forms was evaluated in triplicates every four weeks by a validated HPLC method (Agilent® 1100, Santa Clara, USA). - Dissolution Test: Dissolution studies were performed on the printed forms, in triplicates, using the USPII paddle method in a Sotax® AT7 apparatus (Allschwil, Switzerland) in HCl 0.1 M medium during 6 h at 50 rpm and 37 °C. - Computerized Tomography (CT)-Scan: Printed forms were scanned with a Skyscan 1172/G (Bruker®, Billerica, Massachusetts, United States). Reconstructions and segmentations were performed on NRecon software (v. 1.7.3.1) to obtain the 3D rendering before measuring surface areas and volumes. RESULTS AND DISCUSSION Drug Amorphisation: The absence of a melting point at 167 °C in the thermograms of the three printed forms indicates that ITZ is in an amorphous form. In addition, the three formulations of printed forms allowed ITZ to be maintained in an amorphous forms during the 9 months of storage. Drug Concentration: ITZ yields ranged from 95% to 105% indicating that no degradation occurred during the HME and 3D printing thermal processes and that ITZ is uniformly distributed throughout the filaments and printed forms. Furthermore, no degradation of ITZ occurred during the 9 months of storage. Drug Dissolution: First of all, the solubility and the drug release rate were improved in all the printed forms produced compared to ITZ in a crystalline form. The influence of polymer composition and infill density of the printed forms on the dissolution rate of ITZ were studied. One graph example is illustrated for each factor, but same observations can be made for the other printed forms. - Influence of the Polymer Composition: In formulation 3, which contains a greater proportion of Kollidon VA64 (45%) than formulation 1 (0%) the amount of ITZ in solution after 2 hours of dissolution test is the lowest. However, formulation 2, which contains a proportion of 22,5% of Kollidon VA64 gives the best solubility profile to ITZ overall. In fact, the variation of the interactions between the components depending on the proportions of polymers can influence the dissolution profile of the drug. Several techniques like Fourier Transform Infrared (FTIR) Microscopy and Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) were used to analyse the affinity between the components as well as the distribution of the components within the printed forms. Results show that ITZ is distributed differentially within the two polymers depending on the ratio of both polymers in the formulations. - Influence of the Infill Density: According to the literature, the drug dissolution mainly depends on the surface area/volume ratio of the printed forms, which were measured using CT-scan (Dr Erwan Plougonven, Pr Angélique Léonard, PEPs, University of Liege). Printed forms with 20% and 50% in-fill densities dissolves faster than printed forms with 80% infill density, because their surface/volume ratio is greater. However, dissolution rate also depends on the penetration of water through the printed form which is easier when the infill density is lower, explaining why tablet with 20% infill density dissolve the fastest. - Comparison with Sporanox®: A solubility profile similar to the one of Sporanox®, which also contains amorphous ITZ, is obtained with the printed form of formulation 2 with an 20% infill density. CONCLUSION Thanks to the association of Affinisol®15 LV and Kollidon®VA64 with ITZ, printed forms with different infill densities were successfully printed and the drug release rate was improved. Both polymer composition and infill density of printed forms influence the dissolution rate of the BCS II drug they contain. The interactions between the components change depending on the proportions of polymers used in the formulations and can influence the dissolution profile of the drug. Therefore, it is important to keep this in mind when formulating solid oral forms by HME and FDM and to study closely the affinity between the components as well as the distribution of the components within the printed forms. In addition, for the first three formulations, the lower the infill density of the printed form is, the higher the porosity and the faster the dissolution rate are. The printed forms from the formulation 2 with an infill density of 20% even have a solubility profile similar to that of Sporanox® which is highly encouraging for future experiments.

– Menegola Júlia, Martin Steppe, and Elfrides E.S. Schapoval. 2007

A dissolution test for tablets containing 20mg of citalopram was developed and validated using a reverse-phase liquid chromatographic method and this dissolution test was applied to compare dissolution profiles. The sink conditions, filters, stability of the drug and specificity on different dissolution media were tested to choose a discriminatory dissolution method which uses USP apparatus 1 with baskets rotating at 50rpm, 900ml of deaerated 0.1M hydrochloric acid (HCl) as the dissolution medium. The quantitation method was also adapted and validated. The parameters of difference factor, similar factor, according to current FDA guidelines, and dissolution efficiency were employed to compare dissolution profiles. The dissolution test developed and validated was adequate for its purposes and could be applied for quality control of citalopram tablets, since there is no monograph to citalopram in tablets, this work can be used to help pharmocopoeias.

– Hassouna, M. E. M., Y. M. Issa, and A. G. Zayed 2012

Dissolution testing is an in vitro technique of great importance in formulation and development of pharmaceutical dosage forms, as it can be used as a substitute for in vivo studies under strictly defined and specified conditions. The main objective of the present study is to conduct the comparative dissolution studies of various brands of same dosage forms and treatment of obtained dissolution data by using ƒ2 to determine whether all the formulations used were equivalent or significantly different. Five different brands of drug containing paracetamol and caffeine from different manufacturers were used in the study, and dissolution testing in different dissolution media viz., water, 0.1 N HCl, phosphate buffer of pH 4.5 and phosphate buffer of pH 6.8 was conducted for 12 tablets from each brand for 60 min. by using dissolution testing apparatus USP type-II. Samples were withdrawn at 10 min. time interval and analyzed for drug content by using HPLC technique. Percent drug release at each time interval was calculated for tablets and the data obtained were treated with statistical technique to meet the FDA requirements for obtaining a waiver of bioavailability and bioequivalence studies.

– Zhang, Jianjun, et al. 2012

The aim of the study was to characterize the biopharmaceutics classification system (BCS) category of apigenin (AP) using intrinsic dissolution rate (IDR) and rat intestinal permeability, and to investigate the intestinal absorption mechanism of AP in rats. In the present investigation, equilibrium solubility and intrinsic dissolution rate (IDR) of AP were estimated in phosphate buffers. Effective intestinal permeability (Peff) of AP was determined using single-pass intestinal perfusion (SPIP) technique in four segments (duodenum, jejunum, ileum and colon) of rat intestine at three concentrations (10, 50 and 100 μg/ml). The aqueous solubility of AP in tested phosphate buffers was very poor with maximum solubility of 2.16 μg/ml at pH 7.5. The IDR of AP was very low with a value of 0.006 mg/min/cm2. The minimum and maximum Peffs determined by SPIP were 0.198 × 10−4 and 0.713 × 10−4 cm/s at jejunum and duodenum site, respectively. In addition, the concentration-dependent permeability behaviour was observed in the duodenum and jejunum, which suggested that AP was transported by both passive and active carrier-mediated saturable mechanism in these two intestinal segments. However, the observed concentration-independent permeability behavior in ileum and colon indicated primarily passive transport mechanism of absorption of AP in the last two intestinal segments. AP was classified as class II drug of the BCS due to its low solubility and high intestinal permeability. AP could be well absorbed in the whole intestine with the main absorption site at duodenum. The absorption of AP in four intestinal segments exhibited different transport mechanisms.

– Usmani, Muhammad Talha, et al. 2023

A taste-masked chewable tablet of ciprofloxacin using ion exchange resin Kyron T-134 for enhancing compliance for the paediatric population was developed. The drug-to-resin ratio was optimized for maximum taste masking by studying the effects of soaking time (X1) and mixing time (X2) on complexation (%) using Central Composite Rotatable Design (CCRD). The resin complexes were characterized by bitterness score, DSC, FTIR, and PXRD. The complex was further formulated and optimized into chewable tablets through full factorial design, The optimized formulation was subjected to a bioequivalence study, and a virtual approach of PBPK modelling was adapted to predict the pharmacokinetics of the drug in the paediatric group. The drug resin ratio of 1:1.5 yielded an optimum drug loading of 99.05%. The optimized formulation shows minimum disintegration time with more than 99% drug release within 30 min. The formulation F-9 was found to be bioequivalent with a geometric mean ratio of C_max, T_max, AUC_0–t, and AUC_0–∞ within 90% CI. It was concluded that quality by design approach can successfully be applied to optimize the drug resin ratio and PBPK modelling is a successful predictive tool for estimating the pharmacokinetics of ciprofloxacin HCl in the paediatric population.

– Guhmann, M., Preis, M., Gerber, F., Pöllinger, N., Breitkreutz, J., & Weitschies, W. 2015

Context: Fast onset of action is prerequisite for acute pain medication. A palatable orodispersible medi-cine of diclofenac providing rapid analgesic effect should improve patient compliance and treatment. Objective: In the present study, diclofenac taste-masked orodispersible tablets (ODTs) with fast release characteristics were developed. Different taste-masking approaches and formulation concepts were screened in vitro for candidate selection. Materials and methods: Diclofenac was used as free acid. Five taste-masked microgranule formulations were prepared by wet granulation and/or coating processes, and compressed to ODTs. Citric acid (pH-modifying agent) and Eudragit® E PO (amino methacrylate copolymer) were used as taste-masking agents. Evaluation criteria were (i) disintegration time, (ii) processability and (iii) in-vitro dissolution profiles in simulated saliva (pH 7.4, 5 mL, 3 min) and compendial pH-change media (paddle, 50 rpm). The prototypes were compared to reference ODTs (without taste-masking). Most suitable ODT prototypes were selected and further evaluated for taste-masking efficiency using an electronic tongue. Results and discussion: In simulated saliva, the drug was slower released from the prototypes (between 1.1% and 15.5%) than from reference ODTs (23.7%). Less dissolved particles are thus expected in vivo for taste perception. Two ODT prototypes showed fast and complete drug release in phosphate buffer. The formulation providing the most efficient taste-masking was selected guided by electronic tongue data. Conclusion: A novel palatable and fast acting diclofenac ODT formulation was successfully developed. Formulation design, development and in-vitro evaluation used in this study may serve as rational approach for manufacturing taste-masked orodispersible dosage forms.

– Costa, Paulo, and Sousa Lobo, J.M. 2001

Reaching nearly perfect sink conditions is very important in the determination of drug dissolution rates. Many times, the only factor that is taken into consideration in achieving sink conditions is the relation between the drug concentration and its solubility. The analytical conditions of the dissolution assay, as well as the dissolution apparatus, stirring speed, and nature and volume of the dissolution fluid may also influence the dissolution results. The main objective of this work was to study the influence of the stirring rate conditions and of the dissolution apparatus in the diltiazem hydrochloride release from tablets. Diltiazem hydrochloride sustained-release (SR) tablets were tested and the following dissolution parameters were evaluated: t10%, t25%, t50%, dissolution time, mean dissolution time (MDT), and dissolution efficiency (DE) at t120, and at t360. To analyze the release mechanism, several release models were tested, such as Higuchi, zero order, first order, Baker-Lonsdale, Hixson-Crowell, Weibull, and Korsmeyer-Peppas. The similarities between two in vitro dissolution profiles were assessed by the similarity factor f2. The in vitro release kinetics of diltiazem hydrochloride sustained-release tablets were evaluated using the USP 2 (paddle) and USP 4 (flow-through) apparatus.

– Sousa, A. S., et al. 2025

The pharmaceutical industry is striving to develop innovative and promising tools, increasingly embracing new data-driven approaches, to understand, improve and accelerate the drug product development process. While extended release (ER) oral formulations offer a number of advantages, including maintenance of therapeutic drug levels, a reduction in dosing frequency, and minimization of side effects, achieving consistent drug release profiles remains a significant challenge. As a critical attribute for drug absorption into systemic circulation, in vitro dissolution testing represents a time-consuming and complex method for the evaluation of such formulations. The main objective of this study was to develop a model for predicting drug dissolution in the quality by design (QbD)-based development of ER oral hydrophilic matrix tablets comprising polyethylene oxide (PEO). Two main modelling approaches are conducted and compared: (i) model screening to fit and compare multiple predictive machine learning (ML) models and then deploy the best model, in this case, artificial neural networks (ANN), and (ii) functional data analysis (FDA) combined with the design of experiments (DoE) that fit a smoothing model to each dissolution curve as a continuous function. A dataset comprising 91 ER matrix tablet formulations was analysed, with the dissolution data split into training, validation, and test sets (70%, 20%, and 10%, respectively). The results demonstrated that both ANN and functional DoE (FDOE) models achieved high similarity with the experimental dissolution profiles, as indicated by f2 values ranging from 48 to 88 for the FDOE and 52 to 88 for ANN. This work highlights the potential of integrating advanced data-driven modelling techniques into ER drug development to enhance dissolution prediction accuracy and streamline the formulation process, thus reducing time and costs.

– Hashem, H. M., Abdou, A. R., Mursi, N. M., & Emara, L. H. 2019

Objective: This study was proposed to evaluate and compare the in vitro dissolution profiles of six Metformin Hydrochloride (MH) market products. Methods: Different dissolution apparatuses (USP apparatus II, IV and beaker method) were used to evaluate the dissolution profiles (in phosphate buffer, pH 6.8) of two immediate release (IR) generic products of Metformin Hydrochloride (MH): Cidophage® 1000 mg (G1, Egyptian market) and Metformin arrow® 1000 mg (G2, French market) with respect to the reference products named Glucophage® 850 mg (R1, Egyptian market and R2, French market). In addition to a generic controlled-release (CR) product; Cidophage Retard® 850 mg (G3) versus the reference product; Glucophage XR® 1000 mg (R3)(both from Egyptian market). Dissolution efficiency (DE) and the similarity factor (f2) were calculated. Weight uniformity, hardness, tablet dimensions and MH content were measured. Results: Results of the three apparatuses showed that MH IR products studied (reference and generics) did not meet the 75% USP 30 specifications for MH dissolved at 30 min. For MH CR products, Glucophage XR® did not fulfill the USP release criteria, while Cidophage Retard® did. USP apparatus IV revealed the highest sensitivity and discriminative capability. Conclusion: Generally, MH IR generics (G1 and G2) might be interchangeable with the innovator product (Glucophage®). However, Cidophage Retard® might not be interchangeable with Glucophage XR®.

– Hurtado y de la Peña, Marcela, et al. 2003

The in vitro dissolution of albendazole from three different commercially available products (200 mg tab-lets) was studied using U.S. Pharmacopeia (USP) Apparatus 2 and USP Apparatus 4 in order to compare the release performance of the drug in two essentially different dissolution systems. For both cases, 0.1 N HCl was used as dissolution medium. Only the reference product and one of the generic products studied met the 80% USP 24 specification for albendazole dissolved at 30 min, using USP Apparatus 2. Although the reference product reached 80% of albendazole dissolved at 30 min when Apparatus 4 was used, the generic products' dissolution performance was markedly reduced in this system. Though dissolution rate was slower using Apparatus 4, the total quantity of albendazole dissolved from the reference product, represented by area under the dissolution profile, was practically the same regardless of the system used. Dissolution kinetics of albendazole was adequately described by Weibull's function for all the products. The dissolution time (td) derived from data fitting to this function showed significant differences among the products studied. Data analysis based on analysis of variance (ANOVA) showed nonequiva-lence among the dissolution profiles of generic products compared with the reference product either with the dissolution vessel system or the flow-through cell, as well as nonequivalence among the dissolution profiles using both apparatuses with the same product. Though differences in the dissolution profiles for generic products against the reference product in both systems were found, USP Apparatus 4 showed higher discriminative capacity in differentiating the release characteristics of the products tested.

– Heigoldt, Ulrich, et al. 2010

The focus of in vitro dissolution testing during early development of modified release (MR) formulations is to provide predictive estimates of drug release in respect to in vivo performance of a drug product. However, there are enormous challenges in MR drug development to establish proper dissolution conditions for a predictive test. To overcome limitations of dissolution testing at constant pH, a modified USP apparatus 2 was developed, combining biphasic dissolution with a pH-gradient in the aqueous dissolution medium. Quasi sink conditions in the aqueous phase were introduced by the removal of dissolved active via distribution to an organic phase. Results from in vitro drug-release studies and in vivo absorption studies of four MR formulations made by different technologies comprising the pH-dependent poorly soluble drugs, dipyridamole and the investigational drug BIMT 17, indicated that dissolution testing using the biphasic approach enabled an improved forecast of the in vivo behavior and bioavailability of modified release formulations compared to conventional dissolution testing at pH 1, pH 5.5, or pH 6.8. It can be concluded that the novel pH-adjusted dissolution test might be a useful tool in early drug development to develop, select, and optimize MR prototypes of Biopharmaceutical Classification System (BCS) II compounds.

– Tenjarla, S. 2015

Introduction Mesalamine (5-aminosalicylic acid; 5-ASA) is recommended first-line therapy for mild-to-moderate ulcerative colitis. Many mesalamine formulations employ a pH-dependent release mechanism designed to maximize drug release in the colon. This study compared the in vitro release of 5-ASA from six commercially available mesalamine formulations at pH levels similar to those typically encountered in the human gastrointestinal tract. Methods The release of 5-ASA from six mesalamine formulations [Mesalazin-Kohlpharma (Kohlpharma, Germany), Mesalazin-Eurim (Eurimpharm, Germany), Mesalazina-Faes (Faes Farma, Spain), Mesalazine EC (Actavis B.V., Netherlands), Mesalazine EC 500 PCH (Pharmachemie B.V., Netherlands); multimatrix mesalamine (Shire US Inc., USA)] was monitored separately at three different pH levels [1.0 (2 h), 6.4 (1 h), and 7.2 (8 h)] using United States Pharmacopeia dissolution apparatus II. The dissolution percentage was calculated as a mean of 12 units for each formulation. Results At pH 1.0 and 6.4, \1 % of 5-ASA release was observed for each of the mesalamine formulations tested. At pH 7.2, complete release of 5-ASA occurred within 1 h for Mesalazine EC and Mesalazine EC 500 PCH, and within 2 h for Mesalazin-Kohlpharma, Mesalazin-Eurim, and Mesalazina-Faes; complete release of 5-ASA from multimatrix mesalamine occurred within 7 h. Little variability in rate of 5-ASA dissolution was observed between tablets of each formulation. Conclusion At pH 7.2, 5-ASA release profiles were variable among the commercially available mesalamine formulations that were tested.

– Medina, Raúl, et al. March 2015

Purpose: To develop a first-order derivative spectrophotometric method for the determination of trimethoprim (TMP) and sulfamethoxazole (SMX) from fixed-dose combination generic products using a flow-through cell technique. Methods: Absorbance measurement was achieved at 247.8 and 257.9 nm for trimethoprim and sulfamethoxazole, respectively. USP Apparatus 4 with 22.6 mm cells, laminar flow at 16 ml/min, and 0.1 N HCl at 37 °C as dissolution medium, were used. Dissolution profiles were compared with modeldependent and independent methods. Results: All the products met the pharmacopeial dissolution criterion (Q ≥ 70 %, at 60 min), except SMX in two products (SC 400 mg and SB1 800 mg) using the flow-through cell (53.62 and 49.74 % dissolved, respectively). Using both USP apparatuses, significant differences in mean dissolution time and dissolution efficiency values were found (p < 0.05). All products were in line with Weibull’s kinetics and significant differences in derived parameters (Td) values were found (p < 0.05). Conclusion: Determination of TMP and SMX by derivative spectrophotometry can easily be em-ployed for dissolution studies using the flow-through cell technique. However, it would be necessary to de-termine correlation with in-vivo test results in order to assure safe interchangeability.

– AlMuhsin, A., Ahad, A., Bin Jardan, Y.A., et al. March 2022

Background: Hypolipidemic agents have been shown to be helpful in the primary and secondary prevention of cardiovascular disease. Most often, statins are prescribed to treat hyperlipidemia. There are a number of statins available in the market today, but atorvastatin is the most widely prescribed. It is essential that the drugs should have the appropriate amount of active pharmaceutical ingredient and meet the necessary physical properties. The main purpose of the study was to evaluate the quality of different marketed brands of atorvastatin calcium tablets available in Saudi Arabia. Methods: In this study, innovator product coded as (AS-1) and five generics brands (coded as AS-2 to AS-6) of atorvastatin tablets 20 mg available in Saudi Arabia were evaluated for in vitro dissolution test, weight variations, friability and hardness tests. The analysis of drug was carried out by “high-performance liquid chromatography” (HPLC) method using C18 column (4.6 × 150 mm, 5 μm). The mobile phase was consisted of acetonitrile and HPLC water (pH 2.1, adjusted with orthophosphoric acid) in ratio of 52:48 v/v, the flow rate was 1.0 ml/min. Atorvastatin was detected at a wavelength of 254 nm. Results: According to the results of the dissolution study, the investigated products released more than 90% of atorvastatin in 15 min. Within 60 min, the brands AS-1, AS-3, AS-5, and AS-6 depicted nearly 100% atorvastatin release, while the brand AS-2 displayed 91.69% drug release. According to our findings, the investigated atorvastatin innovator (AS-1) and generic brands such as AS-2 to AS-6 were of good pharmaceutical quality. Conclusions: All generic brands of atorvastatin tablets available in the Saudi Arabian market met the pharmacopoeia's consistency checks such as weight variation, friability, hardness and in vitro dissolution. Hence, focusing on their in vitro release properties, it was determined that these brands could be used interchangeably.

– Tomaz Einfalt, Pascal Detampel, Daniel Häussinger, et al. March 2021

Hydroxychloroquine (HCQ) is a quinoline derivate used for the treatment of malaria and rheumatoid disorders. During early phases of the SARS-CoV2 (COVID-19) pandemic, preliminary and later not substantiated reports suggested that HCQ might benefit COVID-19 patients. This had sparked a worldwide and rapidly rising demand for HCQ drug products. Consequently, patients with pre-existing rheumatic diseases in Switzerland were confronted with an acute drug shortage.We have therefore designed, produced and characterized a generic HCQ drug formulation. The proposed HCQ formulation can be manufactured by using a minimal number of operation steps (mixing, wet granulation, sieving, blending, compression) and readily available pharmaceutical excipients. HCQ tablets were manufactured by granulation of the active pharmaceutical ingredient (API), blending with the external phase and compaction using a non instrument-ed single punch tablet press. Analytics and identification of the API was performed by a combination of NMR, ESI-MS, FTIR and HPLC. HCQ tablets met the quality criteria for an immediate release HCQ dosage form. We hope that free access to non-proprietary protocols covering analytical procedures, formulation design, and manufacturing instructions for HCQ tablets will help to bridge existing and future supply chain gaps.

– Lopez, Jose Raul Medina, et al. May 2019

Objective: Due to quality of generic formulations depends on available information of reference drug products the aim of this work was to perform an in vitro dissolution study of two doses of propranolol-HCl and ranitidine-HCl reference tablets using USP basket or paddle apparatus and flow-through cell method.

Methods: Two doses of propranolol-HCl (10-mg and 80-mg) and ranitidine-HCl (150-mg and 300-mg) of Mexican reference products were used. Dissolution profiles of propranolol-HCl were obtained with USP basket apparatus at 100 rpm and 1000 ml of 1% hydrochloric acid. Profiles of ranitidine-HCl were deter-mined with USP paddle apparatus at 50 rpm and 900 ml of distilled water. All formulations were also studied with the flow-through cell method using laminar flow at 16 ml/min. Dissolution profiles were compared by model-independent (f₂ similarity factor, mean dissolution time and dissolution efficiency) and model-dependent methods (dissolution data adjusted to some mathematical equations). Time data, derived from these adjustments, as t_50%, t_63.25%, and t_85% were used to compare dissolution profiles.

Results: With all approaches used and being high solubility drugs significant differences were found between low and high doses and between USP dissolution apparatuses (*P<0.05).

Conclusion: In vitro dissolution performance of two doses of propranolol-HCl and ranitidine-HCl was not expected. Considering the same USP dissolu-tion apparatus, the reference tablets did not allow the simultaneous release of the used doses. The re-sults could be of interest for pharmaceutical laboratories or health authorities that classify some drug products as a reference to be used in dissolution and bioequivalence studies.

– Reyes-Ramirez, Felipe Dino, Y. A. Vera-Angeles, And Jose Raul Medina-Lopez 2025

Objective: To estimate the hypothetical in vivo behaviour of carbamazepine tablets (immediate-release, 200 mg) with dissolution data and a convolutional approach.

Methods: USP apparatus II and IV and media at pH 1.2, 4.5, and 6.8 (all containing 1% sodium lauryl sulfate) were used. The dissolved drug was calculated from 10 to 60 min. The dissolution profiles were compared with f₂ data and some dissolution parameters. In vitro release data were adjusted using several mathematical models. Predicted plasma levels were calculated using dissolution data and published pharmacokinetic information. A criterion for prediction error<10% for peak plasma concentration and area under the curve is considered suitable.

Results: After 60 min, with both USP apparatuses, all formulations released>75%. Similar dissolution profiles, with all formulations using USP apparatus II at pH 4.5 and 1.2 and with USP apparatus IV at pH 1.2, were found (f₂>50). In almost all the comparisons, dissolution parameters were statistically significant different (*P <0.05). Due to the diversity of the fitting results, no comparisons were made. Prediction errors<10% were found for all formulations using USP apparatus II at pH 4.5 and reference using USP apparatus IV at pH 6.8 and 4.5.

Conclusion: USP apparatus IV showed good discriminatory capacity; however, better in vivo predictions were obtained with USP apparatus II. Corroborating our findings from human studies using the formulations used is necessary.

– Lopez, Jose Raul Medina, et al. August 2019

Objective: To perform an in vitro equivalence study of two doses of carbamazepine reference tablets sold in the local market under hydrodynamic conditions of USP Apparatus 4, a dissolution apparatus that better simulates the human gastrointestinal tract. Results were compared with dissolution official conditions using USP Apparatus 2.

Methods: Dissolution profiles of both formulations were carried out with an automated USP Apparatus 2 at 75 rpm and 900 ml of dissolution medium. USP Apparatus 4 with laminar flow at 16 ml/min and 22.6 mm cells were used. 1% lauryl sulfate aqueous solution at 37.0±0.5 °C was used as dissolution medium. Spectrophotometric determination of drug at 285 nm was carried out during 60 min. Dissolution profiles were compared with model-independent and-dependent approaches.

Results: When comparing dissolution profiles of low vs. high dose similar profiles were found (f₂>50) in each USP dissolution apparatus, however, when the same dose was compared, USP 2 vs. USP 4, opposite results were obtained. Comparison of mean dissolution time and dissolution efficiency data corroborates these results. Weibull function was the best mathematical model that described the in vitro dissolution performance of carbamazepine. No significant differences were found in Td values (low vs. high dose) but opposite results were also found with USP 2 vs. USP 4.

Conclusion: Equivalent dissolution performance of two doses of carbamazepine reference tablets were found in each USP dissolution apparatus. The main problem identified in this comparative study is the low dissolution rate and extent found with USP Apparatus 4. More research on this field is necessary for all available doses of reference drug products since the quality of generic formulations depends on the quality of references.

– Lopez, Jose Raul Medina, et al. August 2021

The aim of this study was to carry out comparative dissolution studies with warfarin sodium reference tablets under the hydrodynamic environments generated by the USP basket and paddle apparatus and flow-through cell using different agitation rates and dissolution media. Methods: Dissolution profiles were obtained with the USP basket and paddle apparatus at 50, 75, and 100 rpm and 900 ml of water as dissolution medium. After this, dissolution profiles of warfarin sodium were obtained with the USP paddle apparatus and flow-through cell method using 0.1 N hydrochloric acid, acetate buffer pH 4.5, phosphate buffer pH 6.8, and water. Spectrophotometric determination at 308 nm was carried out during 30 min. Dissolution profiles were compared with model-independent and model-dependent approaches. Results: Significant differences were found with mean dissolution time and dissolution efficiency at 50 and 75 rpm (*P<0.05) excepting percent dissolved at 30 min with 0.1 N hydrochloric acid and phosphate buffer pH 6.8. Conclusion: More research is necessary to identify the in vitro release performance of poorly soluble drugs under available USP apparatuses considering factors as agitation rate and kind of dissolution media. The knowledge of the in vitro release performance of reference drug products is important for the design of better generic formulations.

– Zhang, T., Liu, Z., Zhang, L., Dai, M., Zhao, H., Xu, H., & Yu, Y, February 2025

Introduction: A method for checking the dissolution of granisetron hydrochloride tablets was established to evaluate its consistency with the in vitro dissolution of the original preparation. Methods: Two fully automated dissolution testers (Agilent and Sotax) were used at 50 rpm with 900 mL of three different pH dissolution media at 37 ± 0.5 °C (pH 1.2 hydrochloric acid, pH 4.5 acetate buffer, and pH 6.8 phosphate buffer). The generic and original preparations of granisetron hydrochloride tablets were analyzed by high performance liquid chromatography. Dissolution rates were determined, and dissolution curve similarity was analyzed for in vitro consistency evaluation. Results: The dissolution method had strong specificity, a linear relationship, no adsorption of the filter membrane, and good precision, accuracy, solution stability, and robustness, all of which satisfied the required specifications for dissolution determination. The generic and original preparations released more than 85% of drug within 15 minutes in all three dissolution media, which is consistent with the dissolution curve of the original drug. Conclusion: The method can be used for in vitro dissolution evaluation and comparison of granisetron hydrochloride tablets.