Development of a Dissolution Test for Extended-Release Bromopride Pellets with In Vivo–In Vitro Correlation

Abstract

The aim of this study was the development of a dissolution test with IVIVC for extended-release bromopride (BPD) pellets using bioavailability data. BPD is a Biopharmaceutics Classification System Class 2 drug, and its absorption is primarily limited by its dissolution rate. Despite this, there are no reports describing a dissolution test for BPD dosage forms. The dissolution medium was selected based upon the sink condition and the gastrointestinal pH. Furthermore, USP Apparatus 1 and 3 were tested, and the dissolution method was compared with that outlined by the manufacturer of the reference drug. Deconvolution by the Wagner-Nelson method was used to obtain the fraction of drug absorbed. The dissolution test that yielded IVIVC for both the fasted and fed states (R 2 > 0.97) and also the discriminative power used Apparatus 1 at 75 rpm in 900 mL of HCl. The dissolution medium (900 mL PBS pH 7.2) was changed after 1 h. Additionally, quantitative analysis was successfully validated by UV absorption (273 nm). Drug release is controlled by the pellet coating and by BPD solubility. The Higuchi release kinetics model best describes the dissolution of commercial BPD pellets batches.

Development of a Dissolution Method for Gliclazide Modified-Release Tablets Using USP Apparatus 3 with <i>in Vitro–in Vivo</i> Correlation

“…This condition, M1, was applied because it comprises most of the pH values from the physiological range and it was also based on other dissolution media compositions described in the literature. 16,37,38) As can be seen in Fig. 4A, differences in the mesh size provided significantly different dissolution profiles ( f 1 >15 and f 2 <50).…”

“…[12][13][14] The selection of dissolution apparatus also plays a key role for the establishment of discriminatory dissolution methodologies. 15,16) The United States Pharmacopeia (USP) Apparatus 3 (Reciprocating cylinder or BioDis) was specifically designed for dissolution evaluation of MR dosage forms because it can mimic physicochemical and mechanical changes experienced by a MR dosage form in the GIT. [17][18][19] In addition, this apparatus demonstrates superior hydrodynamic controls in comparison to USP apparatuses 1 and 2 and provides numerous options in terms of instrumental parameters, such as composition of the media, pH and agitation rate.…”

Development of USP Apparatus 3 Dissolution Method with IVIVC for Extended Release Tablets of Metformin Hydrochloride and Development of a Generic Formulation

“…A programmed drain time of 10 s was set for the process of transferring to the next row of vessels containing new media. 11) Aliquots of 5 mL were manually collected hourly without media replacement for 10 h using a 10 µm cannula filter. For sampling, the cylinders were held above the dissolution medium for 30 s. Samples were filtered through a 0.45 µm membrane, diluted and quantified by UV as described above.…”

“…Linear regressions were calculated using Microsoft Office Excel 2010. 11) Formulation of Generic Tablets A wet granulation method was used to formulate various tablets wherein the granules were produced using different matrices to obtain ER systems. The materials used included the clays Viscogel S4, S7 and B8, lipid matrices containing glyceryl monostearate, stearic acid and cetostearyl alcohol and lipid matrices associated to HPMC.…”

“…This apparatus provides more adequate hydrodynamic conditions compared to USP 1 and 2, and can better mimic the various conditions of the GIT. 9,10) Therefore, the goal of this work was to develop an in vitro dissolution methodology for MTF ER tablets using USP 3 based on IVIVC. In addition, the method that showed the highest level of IVIVC was used as a tool to assist in the development of generic ER formulations for MTF using a lipophilic matrix system.…”