Design and evaluation of controlled onset extended release multiparticulate systems for chronotherapeutic delivery of ketoprofen

Abstract

An oral controlled onset extended release dosage form intended to approximate the chronobiology of rheumatoid arthritis is proposed for site-specific release to the colon. The multiparticulate system consisting of drug-loaded cellulose acetate cores encapsulated within Eudragit S-100 microcapsules was designed for chronotherapeutic delivery of ketoprofen. Drug-loaded cellulose acetate cores were prepared by emulsion solvent evaporation technique in an oily phase at different drug:polymer ratios (1:1, 2:1 and 4:1). These cores were successfully microencapsulated with Eudragit S-100 following the same technique at the core:coat ratio of 1:5. Scanning electron microscopy (SEM) revealed that the cellulose acetate cores were discrete, uniform and spherical with a porous and rough surface, whereas the Eudragit microcapsules were discrete and spherical with a smooth and dense surface. In vitro drug release studies of the Eudragit microcapsules were performed in different pH conditions following pHprogression method for a period of 16 h. The release studies indicated that the microcapsules posses both pHsensitive and controlled-release properties, showing limited drug release below pH 7.0 (6.40 to 8.94%), following which the cellulose acetate cores effectively controlled the drug release for a period of 11 h in pH 7.5. The differential scanning calorimetric and powder X-ray diffraction studies demonstrated that ketoprofen was present in dissolved state in the cellulose acetate polymeric matrix, which could explain the controlled drug release from the cores. The release of ketoprofen from Eudragit microcapsules in pH 7.5 depended on the cellulose acetate levels and was characterized by Higuchi's diffusion model.

Preparation, solid state characterization and evaluation of ketoprofen-glucosamine HCl solid dispersions

“…The same peaks were present in the diffractograms PM and SD but with low intensities, indicating the conversion of crystalline form of pure Ketoprofen to amorphous form in presence of PM and SDs. Moreover, the peak intensity of Ketoprofen was much more reduced as compared to pure Ketoprofen and PM, as shown in Figure 3b-c. Our results con irm the indings of other researchers [17][18][19][20]. …”

“…The SEM analysis showed that relatively smaller polyhedral crystalline forms of Glucosamine and Ketoprofen are clearly visible in PM, as shown in Figure 4c, the Ketoprofen has smallest, irregular, circular and plate like crystals in SDs, which are responsible for enhanced dissolution rate. Similar studies were conducted [17,20]. Our results con irm their indings.…”

“…The characteristics stretching band of pure ketoprofen with Glucosamine in PM and SDs did not change, and on the basis of these observations no possible interaction was observed between Ketoprofen and Glucosamine HCl. The same indings were observed by other researchers [20].…”

Sustained release microspheres of ropinirole hydrochloride: Effect of process parameters

“…All batches were prepared in triplicate. This method was developed on the basis of practical observations, which are discussed in the later part by carrying out certain modifications to the existing methods (10,11).…”

Polymethacrylate Microparticles Gel for Topical Drug Delivery

“…In general, MPs showed no surface-deposited drug crystals and a rough uneven surface with deep grooves. Surface characteristics of MPs are the result of the interplay of preparation conditions including the emulsification method (35) and solvent type (36). Differences in morphological characteristics of MPs made of Eudragit RS100 and L100 could be attributed to differences in viscosity and solvent evaporation rate from their respective solutions in addition to potential interaction of the anionic Eudragit L100 with VRP (37).…”