Solubility-Modulated Asymmetric Membrane Tablets of Triprolidine Hydrochloride: Statistical Optimization and Evaluation

Abstract

Abstract. The aim of the present study was to develop asymmetric membrane (AM) tablets for controlled delivery of highly water-soluble antihistaminic drug triprolidine hydrochloride. The solubility of triprolidine hydrochloride was modulated through the incorporation of coated sodium chloride crystals encapsulated with asymmetric membrane coating polymer, cellulose acetate butyrate. Formulation of AM tablets was based on a 2 3 factorial design to study the effect of formulation variables, namely, polymer concentration, level of pore former, and amount of osmogen on the in vitro release. Core tablets prepared by wet granulation and coated with asymmetric membrane by a dip coating method were evaluated. Statistical analysis was done with the Design Expert Software 8.0.2 (USA), and the polynomial equation generated by Pareto charts was used for validation of the experimental design. The interaction chart and response surface plots deduced the simultaneous effect of independent variables on in vitro drug release. The in vitro drug release was inversely proportional and directly related to the level(s) of polymer and pore former in the membrane, respectively. The level of osmogen not only increased the osmotic pressure but also controlled the drug release due to a common ion effect. The drug release of the optimized formulation (F6) followed zero-order kinetics, which would be capable of reducing the administration, and was stable over 3 months. SEM photographs revealed asymmetry in membrane structure.KEY WORDS: asymmetric membrane; coated sodium chloride; cellulose acetate butyrate; solubility modulation; 2 3 factorial design.

Osmotically Regulated Floating Asymmetric Membrane Capsule for Controlled Site-Specific Delivery of Ranitidine Hydrochloride: Optimization by Central Composite Design

“…The results concluded that, when osmogen and pore former were at high levels in FAMC6 and FAMC8, higher release (average release,~92%) was observed than FAMC1 and FAMC2 (average release,~85%), having lower levels of both variables. The effect is attributable to the combined result of increased perforation of the capsular wall and osmotic gradient that has been documented in our previous studies (8)(9)(10)(11). Fig.…”

“…The incorporation of higher amount of coated NaCl (FAMC4, FAMC6, FAMC7, and FAMC8) resulted in the development of significant osmotic pressure inside the capsular core, and at the same time, the presence of the common ion Cl − reduced the solubility of RHCl that could have resulted in decreased release of RHCl. However, the generation and maintenance of the osmotic gradient for a longer duration due to the coated NaCl crystals counteracted the suppression in release (11), and hence, higher drug release was observed at 12 h from these formulations (~93%) when compared to the formulation made with lower levels of coated NaCl (FAMC1, FAMC2, FAMC3, and FAMC5) that displayed release to the order of~87% in 12 h.…”

“…Hence, a solubility modulator (coated NaCl) was used. This approach (based on the common ion effect) has been utilized by us in the development of AMCs of highly water-soluble drugs-phenylephrine hydrochloride (10) and triprolidine hydrochloride (11).…”

“…As the drug delivery system is expected to release 100% drug in 12 h, we were looking for a formulation component that would help in achieving 50% drug release in 6 h. Based on this preliminary experimentation, NaCl coated with 3% w/v CA 398-10 as solubility-modulating agent in the AMC formulation would accomplish a drug release approximating 100% in 12 h. Other coat strengths displayed a %CDR either above or below 50% in 6 h. Predicatively, either the entire drug may get released before 12 h (in case of 1% w/v and 2% coat strength) or it may exceed 12 h with 4% coat strength. This suggests the importance of coat thickness on the solubility modulator crystals for achieving the desired release (11).…”

“…Research inputs from our group have resulted in the successful development of AMCs of drugs with varying water solubility, namely, ketoprofen (6,7), flurbiprofen (8), promethazine hydrochloride (9), phenylephrine hydrochloride (10), and triprolidine hydrochloride (11), thus proving the efficacy of the system for both poorly water-soluble and highly watersoluble drugs. The present work aims at exploring the feasibility of AMCs for site-specific osmotically regulated delivery of ranitidine hydrochloride (RHCl) as a floating single-unit device.…”