Formulation and Development of Gastroretentive Dipyridamole Microspheres: Proof of Concept by In vitro-In vivo Assessment

Abstract

Vanshiv, et al.: Gastroretentive Dipyridamole MicrospheresThe present research was aimed at development and optimization of dipyridamole gastroretentive microspheres. Gastro retention was achieved using swellable polymeric material such as hydroxypropyl methylcellulose K4M, ethyl cellulose as release retardant using solvent diffusion evaporation method. 3 2 factorial design was applied for the development of best optimized formulation. The design was developed by considering two independent variables, ethyl cellulose, and stirring speed. Their effect on drug release, entrapment efficiency, particle size was analysed using response surface methodology. Formulation B1 among all formulations tested was found to be the best as it demonstrated prolonged floating time, maximum entrapment efficiency and drug release in a controlled manner. Formulation B1 was characterized further for presence of residual solvent by gas chromatography/mass spectrometry and the result showed absence of residual solvent. Gastro retention was assessed using the in vivo gamma scintigraphy technique in albino rabbits and the results indicated prolonged gastric retention. Pharmacokinetic study comparing pure dipyridamole and dipyridamole microspheres was conducted and C max , T max and K el were estimated. In vitro-in vivo correlation was determined using Wagner-Nelson function. Pharmacokinetic study revealed improved bioavailability (30 %) as compared to pure dipyridamole. Good correlation was obtained with a regression coefficient of 0.9704. The in vivo gamma scintigraphy and pharmacokinetic studies confirmed gastric retention of the prepared dipyridamole floating microspheres. Accelerated stability studies indicated integrity of the developed formulations.

Polymeric Excipients in the Technology of Floating Drug Delivery Systems

“…Hollow granules (ionotropic gelation) Chitosan [25] Granules (ionotropic gelation) NA, Carrageenan [28] NA, Eudragit RL100 [85] Chitosan [26] Pectin [30] NA conjugate with bovine serum albumin [37] Hollow microspheres (solvent removal) EC [47] EC, HPMC E5 [50] EC, HPMC E50 [86] Eudragit S-100 [71] Eudragit S-100 [72] Acrycoat S 100 [74] Combination of Eudragit L100 and Eudragit RS100 [73] Polycarbonate, Polypropylene Glycol PFA [83] HPMC 3K, Eudragit RS PO [87] EC (10 cP), PVP [88] Microspheres (solvent removal) EC [89] EC, HPMC K4M [90] CA [62] Microspheres ("multiple emulsion method", solvent removal) EC, PVP [91] Tablets (direct compression) HPMC K4M, Camphor SA [55] Tablets (wet granulation) Locust bean gum, Camphor SA [41] HPC (Klucel LF), PEO (Polyox WSR N 60 K), Menthol SA [92] Tablets (shaping and freeze drying) EC, HPMC (100 cP) [49] Tablets (FDM 3D printing) HPC [60] HPMC acetate succinate, PEG 400 [93] HPC, PVP [94] Tablets (Tablet-core-direct compression; body-FDM 3D printing) HPC, EC [59] PLA [81] EVOH, HPMC K15M [65] Tablets (SLS 3D printing) Nylon [82] Cylindrical extrudate (3D printing with simultaneous ionotropic gelation) NA [23] Hydrogel (ionotropic gelation) Graft copolymer of chitosan and PVP [27] Nanofiber (electrospinning) PLA [64] Pellets or cylindrical extrudates (extrusion) Eudragit RSPO, HPMC K15 M, Ethanol PFA [95] Modular gastro-renal delivery system (wet granulation and compression) HPMC K15 M, PEG 6000, PVP K30…”