Dissolution Testing of a Controlled-Release Capsule Formulation: Challenges and Solutions Using a Semi-Automated Dissolution System

Abstract

A controlled-release formulation was developed using enteric-coated beads in a hard gelatin capsule shell. This formulation requires two-stage dissolution testing at low and neutral pH. Because of high toxicity and limited stability of the active pharmaceutical ingredient in aqueous solution at room temperature, it is preferable to limit the analyst's contact with the sample solutions during testing, and aliquots from the dissolution vessel need to be quickly filtered and refrigerated immediately after sampling. To meet these challenges, a semi-automated dissolution method was developed and validated. Dissolution samples are withdrawn and filtered into vials in the HPLC sample compartment where the temperature is controlled at 4 °C. A fast HPLC method was developed with a 3-min run per injection, enabling analysis of the samples within a very short time after collection, thereby decreasing the sample storage time and potential for degradation. An evaluation was also conducted for comparison of serial and parallel operation of two dissolution baths for the two-stage testing. Serial operation was chosen for this method and applied with a medium-exchange technique, which is safe, robust, easy to perform, compliant with USP, and gives enhanced productivity.

Rapid profiling of enteric coated drug delivery spheres via Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS)

“…3 The dissolution testing of these formulations can also be problematic when the potency/toxicity of the API is high. 4 There are three commonly used types of enteric coatings, namely, polymethacrylates, cellulose esters and polyvinyl derivatives. In this study, a prescribed drug product Lanzol is investigated which contains enteric coated drug delivery spheres.…”

Challenges of Dissolution Methods Development for Soft Gelatin Capsules

“…The quality of the SGCs dosage form is ensured by meeting the USP acceptance criteria for the acid stage, i.e., less than 10% of the API is released from the drug product during the first step of the developed dissolution technique, and therefore, the coating is considered to have passed the acid-step test. If each unit release is not less than Q + 5% for the buffer stage, then the soft gel dosage form has passed the second step of dissolution [125]. Q represents the amount of an active ingredient dissolved in the dissolution medium, expressed as a percentage of the labelled content.…”

“…Q represents the amount of an active ingredient dissolved in the dissolution medium, expressed as a percentage of the labelled content. To overcome the challenges of manual manipulations of adding the buffer solutions and adjusting the pH during the two-step dissolution testing, other research groups have developed semi-automated dissolution systems for these measurements [125]. The media exchange technique is challenging for SGCs, especially if the capsules have softened due to the liquid exposure, soaking alone will cause some softening but may not cause the rupture of the capsule.…”

Preparation of Diatomite-Chitosan Composites for Loading and Release of Diphenhydramine HCl

“…The basket method (USP Apparatus I) was used in the release studies of formulations filled into capsules. This method is a frequently used dissolution for capsule formulations (Kumar et al, 2012;Lo et al, 2013;Damian et al, 2021). As shown in Figure 7, with the disintegration of the capsule wall depending on the temperature and medium, the DPH passed into the release medium from the 5 th minute.…”