Improved compressibility, flowability, dissolution and bioavailability of pioglitazone hydrochloride by emulsion solvent diffusion with additives.

Spherical agglomerates of pioglitazone hydrochloride were prepared by the emulsion solvent diffusion method with additives (polyethylene glycol 6000, polyvinyl pyrrolidone, beta cyclodextrin, eudragit RS100, low acyl gellan gum and xanthan gum) using methanol, chloroform and water as a good solvent, bridging liquid and poor solvent respectively. Prepared agglomerates were evaluated for compressibility, solubility, dissolution rate and bioavailability, and characterized by SEM, XRPD, DSC and FTIR spectroscopy. Particle size, flowability, compactibility, packability, solubility, dissolution rate and bioavailability of plain agglomerates and agglomerates with additives (except with polyvinyl pyrrolidone) were advantageously improved compared with raw crystalline pioglitazone hydrochloride. These improved properties for direct compression were due to their large-spherical shape and enhanced fragmentation during compaction, together with increased tensile strength and reduced elastic recovery of the compacts. XRPD and DSC studies indicated polymorphic transition of pioglitazone hydrochloride from form II to I during recrystallization but this was not associated with any chemical transition, as indicated by FTIR spectra, well supported by stability studies. Thus spherical crystallization by the emulsion solvent diffusion method with selected additives is a satisfactory method for direct tableting of pioglitazone hydrochloride giving improved bioavailability.

Permeation enhancers in the transmucosal delivery of macromolecules.

The present article presents a compilation of information regarding various chemical permeation enhancers useful for transmucosal delivery of macromolecules. In the recent past, biotechnology has provided a great number of macromolecules for treatment of various disorders. With the rise in importance of macromolecules, especially proteins and peptides, an enormous volume of research on various novel routes of drug delivery has been carried out. Inspite of its giving the highest and fastest bioavailability, the parenteral route is not a preferred option, due to its inconvenience and the noncompliance of patients. Mucosal surfaces are the most common and convenient routes for delivering drugs to the body. However, macromolecular drugs such as peptides and proteins are unable to overcome the mucosal barriers and/or are degraded before reaching the blood stream. Transmucosal drug delivery with various bioavailability enhancers is receiving increasing attention as a possible alternative to parenteral delivery of macromolecules. Among the various bioavailability enhancers, chemical permeation enhancers have been most studied. Permeation enhancers reversibly modulate the permeability of the barrier layer in favor of drug absorption. Newer permeation enhancers like zonula occludin toxin, poly-L-arginine, chitosan derivatives etc have shown a significant increase in drug absorption through transmucosal routes without serious damage to the barrier layer. In particular delivery of macromolecules via the nasal and pulmonary routesusing newer permeation enhancers has emerged as a possible alternative to the parenteral delivery ofmacromolecules.

Preparation and characterization of glassy celecoxib.

Celecoxib, a poorly water-soluble drug, was converted into a glassy state by melt quenching. The properties of glassy celecoxib were studied using infrared (IR) spectroscopy, differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), intrinsic dissolution rate (IDR), and thin-layer-chromatography (TLC). Glass transition occurred at 51.8 degrees C. Infrared spectrum of glass has revealed significant changes due to H-bonding. Celecoxib glass shows around 15 times faster dissolution as compared with the crystalline state. Heckel plot analysis has shown better compressibility in glassy state. Unpulverized glass remained stable for 3 months, whereas after pulverization about 70% crystallinity was gained in 100 hours. Further attempts may be carried out to stabilize the glass.

Spherical crystallization of celecoxib.

Celecoxib exhibits poor flow properties and compressibility. Spherical crystallization of celecoxib was carried out using the solvent change method. An acetone:dichloromethane (DCM):water system was used where DCM acted as a bridging liquid and acetone and water as good and bad solvent, respectively. Hydroxypropylmethylcellulose (HPMC) was used to impart strength and sphericity to the agglomerates. The effect of amount of bridging liquid and speed of agitation was studied using 3(2) factorial design. Primary properties of the agglomerates were evaluated by infrared spectroscopy, powder X-ray diffraction, and differential scanning calorimetry. The effect of variables on micromeritic, mechanical, compressional, and dissolution behavior was evaluated by response surface methodology. Particle size, bulk density, mean yield pressure (MYP), and drug release were found to be significantly affected by either of the two variables. Interaction of variables significantly affected the MYP.