Gel Strength of Hydrophilic Matrix Tablets in Terms of In Vitro Robustness

Purpose The purpose of this study was to correlate the gel strength of swollen matrix tablets with their in vitro robustness against agitation intensity and applied mechanical forces. Five commercial products, i.e. Glucophage®, Alfuzosin®, Tromphyllin®, Preductal® MR and Quetiapin® formulated as water-soluble/erodible matrix tablets were investigated. Methods Effect of agitation speed (50–150 rpm) on drug release, hydration/erosion and gel strength was investigated using USP paddle apparatus II. The gel strength of matrix tablets during dissolution at different conditions was characterized by a texture analyzer. Results Commercial tablets formulated with HPMC of higher viscosity, such as K15M or K100M, demonstrated the gel strength in swollen state >0.02 MPa. In this case, the release mechanism was predominantly diffusional and, therefore, not affected by stirring speed and mechanical stress. In contrast, the Quetiapin® matrix tablet, formulated with HPMC K 4 M in amount of approx. 25%, demonstrated the gel strength dropped below 0.02 MPa after 6 h of release. In this case, the drug was predominantly released via erosional mechanism and very susceptible to stirring speed. Conclusion Sufficient gel strength of swollen tablets is an important prerequisite for unchanged in vitro performance in consideration of mechanical stress.

COMPARATIVE DISSOLUTION STUDIES OF WARFARIN SODIUM TABLETS: INFLUENCE OF AGITATION RATE, DISSOLUTION MEDIUM, AND USP APPARATUS

Objective: 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). Makoid-Banakar was the best-fit model used to describe the in vitro release performance of warfarin sodium with 50-100 rpm and the USP basket and paddle apparatuses. Significant differences in all calculated parameters were found (*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

Enteric Hard Capsules for Targeting the Small Intestine: Positive Correlation between In Vitro Disintegration and Dissolution Times

In this study, the potential for correlation between disintegration and dissolution performance of enteric-coated (EC) dosage forms was investigated. Different enteric hard shell capsule formulations containing caffeine as model drug were tested for disintegration (in a compendial disintegration tester) and for dissolution in both USP type I (basket) and type II (paddle) apparatuses using different media. Overall, good correlations were obtained. This was observed for both the basket and the paddle apparatus, indicating that the use of disintegration testing as a surrogate for dissolution testing (allowed by International Conference on Harmonization (ICH) for immediate release dosage forms in case, in addition to other conditions, a correlation between disintegration and dissolution is proven) could be extended to include delayed release dosage forms.

Influence of Acetylated Annealed Starch on the Release of β-Escin from the Anionic and Non-Ionic Hydrophilic Gels

Naturally sourced products introduced to human nutrition and rediscovered for therapy include polysaccharides from potatoes. The starch may obtain unique properties via acetylation with acetic anhydride at 13 cm3/100 g of starch as the basic dose of reagent used in industrial conditions. The hydrogel formulation was applied as a carrier for escin included in the dry extract of Aesculus hippocastanum. Six hydrogels were evaluated (methylcellulose, polyacrylic acid-Carbopol 980 NF and polyacrylate crosspolymer 11—Aristoflex Velvet) with various concentrations of the modified starch. The kinetic studies of in vitro β-escin release were carried out in purified water at 37 ± 0.5 °C using a paddle apparatus at 50 rpm and a time period of 7 h. The criterion for the most suitable model was based on a high correlation coefficient of evaluated release profiles. The addition of modified annealed acetylated potato starch resulted in prolongation of β-escin release.

Investigation to Explain Bioequivalence Failure in Pravastatin Immediate-Release Products

The purpose of this work is to explore the predictive ability of the biopharmaceutics classification system (BCS) biowaiver based on the dissolution methods for two pravastatin test products, where one of them showed bioequivalence (BE) while the other test failed (non-bioequivalence, or NBE), and to explore the reasons for the BE failure. Experimental solubility and permeability data confirmed that pravastatin is a BCS class III compound. The permeability experiments confirmed that the NBE formulation significantly increased pravastatin permeability, and could explain its higher absorption rate and higher Cmax. This finding highlights the relevance of requiring similar excipients for BCS class III drugs. The BCS-based biowaiver dissolution tests at pH 1.2, 4.5, and 6.8, with the paddle apparatus at 50 rpm in 900 mL media, were not able to detect differences in pravastatin products, although the NBE formulation exhibited a more rapid dissolution at earlier sampling times. Dissolution tests conducted in 500 mL did not achieve complete dissolution, and both formulations were dissimilar because the amount dissolved at 15 min was less than 85%. The difference was less than 10% at pH 1.2 and 4.5, while at pH 6.8 f2, results reflected the Cmax rank order.

In vitro Pharmaceutical Equivalence Study of Three Brands of Atenolol Tablets Available in Bangladesh

The aim of the present work was to assess the pharmaceutical equivalence of three brands of atenolol (50 mg) tablets available in Bangladesh using in vitro dissolution study. The dissolution study was carried out using the paddle apparatus according to the guidelines of United States Pharmacopoeia (USP). The dissolution profiles of three locally manufactured atenolol tablets were determined and compared with the dissolution profile of atenolol tablet from innovator’s company. All samples attained more than 85% dissolution within 10 minutes. Mean dissolution values were employed to estimate difference factor (f1) and similarity factor (f2). Difference factor (f1) and similarity factor (f2) were used to assess in vitro bio-equivalency among the three brands. Other general quality assessment parameters such as hardness, friability and disintegration time were also determined. All brands complied with the official specifications for hardness, friability and disintegration time. The study indicated that all brands can be prescribed interchangeably. Dhaka Univ. J. Pharm. Sci. 18(1): 43-48, 2019 (June)

INFLUENCE OF DOSE AND USP DISSOLUTION APPARATUS IN THE RELEASE PERFORMANCE OF REFERENCE TABLETS: PROPRANOLOL-HCl AND RANITIDINE-HCl CASES

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 determined 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 t50%, t63.25%, and t85% 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 dissolution apparatus, the reference tablets did not allow the simultaneous release of the used doses. The results 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.

DISSOLUTION PERFORMANCE OF MELOXICAM FORMULATIONS UNDER HYDRODYNAMICS OF USP PADDLE APPARATUS AND FLOW-THROUGH CELL METHOD

Objective: To study the in vitro dissolution performance of four generic formulations of the poorly soluble drug meloxicam and the reference under hydrodynamic environments generated by flow-through cell method and USP paddle apparatus (pharmacopeial test). Methods: Dissolution method was validated according to ICH guidelines. Dissolution profiles were carried out with an automated flow-through cell apparatus (laminar flow at 16 ml/min with 22.6 mm cells) and USP paddle apparatus at 75 rpm. Phosphate buffer pH 7.5 at 37.0±0.5 °C was used as dissolution medium. Spectrophotometric determination of drug at 362 nm was carried out during 30 min. Dissolution profiles were compared with model-dependent and-independent methods. Results: Practically, all generic formulations showed significant differences with the percentage of drug dissolved at 30 min, mean dissolution time and dissolution efficiency, when USP paddle apparatus was used (*P<0.05), while only two generic formulations were different to reference using flow-through cell method. After adjustment to different mathematical equations, Weibull function was the best model to describe meloxicam dissolution performance and significant differences were found with all drug products when USP paddle apparatus was used, while only one formulation was different with flow-through cell method. Conclusion: The study reveals the need to look for better dissolution schemes for meloxicam tablets since USP paddle apparatus may not reflect properly the in vitro dissolution performance of meloxicam generic formulations and reference.

DEVELOPMENT AND VALIDATION OF SPECTROSCOPIC METHODS FOR SIMULTANEOUS ESTIMATION AND DISSOLUTION OF OFLOXACIN AND ORNIDAZOLE IN TABLET DOSAGE FORMS

The aim of this work was to develop and validate simple, accurate and precise spectroscopic methods (multicomponent, dual wavelength and simultaneous equations) for the simultaneous estimation and dissolution testing of ofloxacin and ornidazole tablet dosage forms. The medium of dissolution used was 900 ml of 0.01N HCl, using a paddle apparatus at a stirring rate of 50 rpm. The drug release was evaluated by developed and validated spectroscopic methods. Ofloxacin and ornidazole showed 293.4 and 319.6nm as λ max in 0.01N HCl. The methods were validated to meet requirements for a global regulatory filing. The validation included linearity, precision and accuracy. In addition, recovery studies and dissolution studies of three different tablets were compared and the results obtained show no significant difference among products.