No abstract

The real issue in the development of oral controlled release dosage forms is not just to prolong the delivery of drugs but also to prolong the presence of dosage forms in the stomach in order to improve the bioavailability of drugs with a 'narrow absorption window'. In the present study, an anti-ulcer drug, ranitidine hydrochloride, is delivered through a gastroretentive ethyl cellulose-based microparticulate system capable of floating on simulated gastric fluid for > 12 h. Preparation of microparticles is done by solvent evaporation technique with modification by using an ethanol co-solvent system. The formulated microspheres were free flowing with good packability and encapsulation efficiencies were up to 96%. Scanning electron microscopy confirmed porous, spherical particles in the size range 300-750 microm. Microspheres showed excellent buoyancy and a biphasic controlled release pattern with 12h. In vivo bioavailability studies performed on rabbits and T(max), C(max), AUC were calculated and confirmed significant improvement in bioavailability. The data obtained thus suggests that a microparticulate floating delivery system can be successfully designed to give controlled drug delivery, improved oral bioavailability and many other desirable characteristics.

Gelatin A microspheres of propranolol hydrochloride for intranasal systemic delivery were developed with the aim to avoid fi rst pass metabolism, to improve the patient compliance, to use an alternative therapy to conventional dosage form, to achieve controlled blood level profi les, and to improve the therapeutic effi cacy of propranolol hydrochloride in the treatment of various cardiovascular disorders and as a prophylactic for migraine. Gelatin A microspheres were prepared by emulsion crosslinking method using glutaradehyde as a crosslinking agent. Gelatin and chitosan were used as polymer and co polymer respectively. All the prepared microspheres were evaluated for physical characteristics, such as particle size, incorporation effi ciency, swelling index, in vitro bioadhesion using rat jejunum and in vitro drug release in pH 6.6 phosphate buffer. Average particle size of microspheres was found to be in the size range 1-50 µm. Increase in drug and polymer concentration in the formulation increased incorporation effi ciency. All the microsphers showed good bioadhesive properties and swelling indices and good sustained release of drug. The data indicates that propranolol hydrochloride release followed Higuchi's matrix and Peppa's model. Stability studies showed stability of formulation at all the conditions to which they were subjected.

Sodium alginate (SA) floating beads containing cefpodoxime proxetil, a third-generation cephalosporin antibiotic, were prepared by precipitation method using calcium carbonate as gas generating agent. Hydroxypropyl methylcellulose (HPMC) was used in all the four formulations in different proportions (F1, F2, F3, and F4) as swelling agent to control the release of the drug. Gas generating agent forms pores on the surface of the beads because of the rapid escape of CO 2 during the curing process in precipitating media. Scanning electron microscopy confirmed their porous and grossly spherical structure, and the size of the beads were in the range of 700-1000 lm. The size of the beads increases with the increase in the concentration of gas-forming agent and decreases with the increase in the concentration SA. The drug entrapment efficiency was found to be in the range of 85.3-91.1%. F2shows least entrapment, whereas F3 shows maximum entrapment. The percentage porosity was 82.1-89.1%, and the mean pore diameter was 0.41-0.52 lm. The porosity depends on the concentration of gas-forming agent. The mechanical strength of the beads was 591-1073 g. All the formulations showed good floating time. The in vitro release was performed in glycine dissolution media according to USP for about 12 h. The cumulative % drug release was found to be 67.5-87.3%. The in vitro dissolution study reveals that the concentration of the gas generating agent and SA affects the release rate.

Ophthalmic nanosuspensions (ONS) have shown a potential for ophthalmic delivery over the conventional ocular formulations. The objective of the study was to assess the effect of surfactants and polymers on particle size and drug release. Sparfloxacin ONS were prepared by optimizing the concentration of HPMC E5 and water soluble chitosan by using solvent diffusion method followed by probe sonication. The Poloxamer 407 and Kolliphor P188 were used as a surfactant. The produced nanosuspensions were characterized for particle size, shape, zeta potential and drug release. The average particle size of the nanosuspension was 300 to 500 nm. The in vitro drug release study showed that the optimized nanosuspension of water soluble chitosan sustained drug release up to 9 h compared to 6 h for the hydroxypropylmethylcellulose (HPMC) nanosuspension. Further, the sparfloxacin ONS formulation showed excellent ocular tolerance and biocompatibility as determined by hen's egg test chorioallantoic membrane (HET CAM) and resazurin assay on Vero cell lines. Moreover, optimized formulation was found to be stable, isotonic, non-toxic with higher in vitro and in vivo antimicrobial potential.