Application of Pharmaceutical QbD for Enhancement of the Solubility and Dissolution of a Class II BCS Drug using Polymeric Surfactants and Crystallization Inhibitors: Development of Controlled-Release Tablets

Abstract

The aim of this study was to apply quality by design (QbD) for pharmaceutical development of felodipine solid mixture (FSM) containing hydrophilic carriers and/or polymeric surfactants, for easier development of controlled-release tablets of felodipine. The material attributes, the process parameters (CPP), and the critical quality attributes of the FSMs were identified. Box-Behnken experimental design was applied to develop space design and determine the control space of FSMs that have maximum solubility, maximum dissolution, and ability to inhibit felodipine crystallization from supersaturated solution. Material attributes and CPP studied were the amount of hydroxypropyl methylcellulose (HPMC; X(1)), amount of polymeric surfactants Inutec®SP1 (X(2)), amount of Pluronic®F-127 (X(3)) and preparation techniques, physical mixture (PM) or solvent evaporation (SE; X(4)). There is no proposed design space formed if the Pluronic® content was below 45.1 mg and if PM is used as the preparation technique. The operating ranges, for robust development of FSM of desired quality, of Pluronic®, Inutec®SP1, HPMC, and preparation technique, are 49-50, 16-23, 83-100 mg, and SE, respectively. The calculated value of f2 was 56.85, indicating that the release profile of the controlled-release (CR) tablet (CR-6) containing the optimized in situ-formed FSM was similar to that of the target release profile. Not only did the ternary mixture of Pluronic®, HPMC with Inutec®SP1 enhance the dissolution rate and inhibit crystallization of felodipine, but also they aided Carbopol®974 in controlling felodipine release from the tablet matrix. It could be concluded that a promising once-daily CR tablets of felodipine was successfully designed using QbD approach.

Follicular delivery of spironolactone via nanostructured lipid carriers for management of alopecia

“…21 The predicted R 2 values were in reasonable agreement with the adjusted R 2 in all responses (approximately 0.2 difference between them) (Table 3). 22,23 Adequate precision measured the signal-to-noise ratio to ensure that the model can be used to navigate the design space. 24 A ratio 4 (the desirable value) was observed in all responses.…”

Continuous Production of Fenofibrate Solid Lipid Nanoparticles by Hot-Melt Extrusion Technology: a Systematic Study Based on a Quality by Design Approach

“…This approach begins with predefined objectives to ensure predictable product quality. The main purpose of QbD is to identify and control critical parameters which affect product quality [1][2][3]. QbD has been promoted by the United States Food and Drug Administration (US FDA) as a way to enhance pharmaceutical development through design efforts from product conceptualization to commercialization [4,5].…”

Experimental and Computational Studies of Physicochemical Properties Influence NSAID-Cyclodextrin Complexation

“…For example, reducing particle size of an active ingredient has been shown to increase the rate of drug dissolution and improve bioavailability (2)(3)(4)(5). Examples of techniques to improve drug solubility include the addition of surfactants (6,7), use of co-solvents (8,9), formulating as amorphous solid dispersions (10,11), and cyclodextrin (CD) complexation (12)(13)(14)(15).…”