-Cyclodextrin

In this study Β-Cyclodextrin facilitated Nanosponges were prepared by the solvent evaporation technique and subsequently formulated in a tablet form for immediate release of Glipizide. The Nanosponges formulations were prepared by solvent evaporation method employing Β-Cyclodextrin as a polymer. The compatibility of the drug with formulation components was established by Fourier Transform Infra-Red (FTIR) spectroscopy. The surface morphology, particle size, production yield, and drug entrapment efficiency of Nanosponges were examined. Shape and surface morphology of the Nanosponges were examined using scanningelectron microscopy. Particle size of prepared Nanosponges was observed in the range of 428.7  to  633.5nm. Scanning electron microscopy revealed the porous, spherical nature of the Nanosponges.SEM photographs revealed the spherical nature of the Nanosponges in all variations; however, at higher ratios, drug crystals were observed on the nanosponge surface. Increase in the drug/polymer ratio (1:1 to 1:3) increased their yield (10.23 ± to 35.69), which is in increasing order due to the increase in the concentration of polymer but after certain concentration it was observed that as the ratio of drug to polymer was increased, the particle size decreased, the drug content of different formulations was found in the range 94.4to 98.6%,the entrapment efficiency of different formulations were found in the range of 82.11 to 94.40%, the drug  release of the Optimized formulation was found to be 97.71%.

Itraconazole is a potent triazole antifungal drug which has low solubility at physiological pH conditions. It is active in vitro against a wide variety of fungi with a spectrum of activity which qualitatively resembles that of ketoconazole, the first oral azole to gain widespread acceptance. Itraconazole binds more avidly to fungal cytochrome P-450 than does ketoconazole and unlike ketoconazole, has little effect on mammalian cytochrome P-450 enzyme systems.The purpose of present work was to explore the feasibility and preparation of the Itraconazole Hydrochloride salt to improve the solubility and dissolution rate of poorly soluble drug Itraconazole. Itraconazole Hydrochloride was synthesized by using addition reaction with hydrochloric acid. Then it was incorporated into a new derivative of cyclodextrins Sulfobutyl ether β-Cyclodextrin (CAPTISOL) and 2-Hydroxypropyl β-Cyclodextrin by using physical mixing, kneading and co-evaporation techniques. The solubility of prepared salt was found multifold than the solubility of itraconazole. The dissolution studies of itraconazole complexes exhibited high percentage drug dissolution than that of the pure drug which can be attributed to the increase in drug solubility provoked by the complexation technique. The results indicated Itraconazole HCL-Captisol (1:2 molar ratio) prepared by kneading method shows better characteristics when compared with pure drug and other formulations.

Ritonavir, exhibits low and variable oral bioavailability due to its poor aqueous solubility. Its oral absorption is dissolution rate limited and it requires enhancement in the solubility and dissolution rate for increasing its oral bioavailability. The individual main and combined  (interaction) effects of CDs and Solutol HS15 on the dissolution rate of  ritonavir from tablet formulations was investigated in a series of 22 – factorial experiments. Ritonavir (100mg) formulated in to compressed tablets by wet granulation method employing selected combinations of CDs ( βCD and HPβCD ) and Solutol HS15. All the tablets prepared were of good quality fulfilling the official (I.P) standards with regard to hardness, friability, disintegration time and drug content. Drug dissolution from the tablets formulated followed first order kinetics and gave relatively higher rates of dissolution (K1) and dissolution efficiency (DE30) values when compared to those of ritonavir plain tablets. Formulations R4 and R8, gave much higher dissolution rates when compared to plain tablets, R1. A 21.35 and 16.85 fold increase in K1 was observed respectively with formulations R4 and R8 when compared to formulation R1 (plain tablets). The dissolution efficiency (DE30) was also increased from 7.29% for formulation R1 (plain tablets) to  43.32 % and 39.36 % respectively for formulations R4 and R8. In combination βCD-Solutol HS15 gave 21.35 fold increase in the dissolution rate HPβCD and Solutol HS15 alone gave an enhancement of 4.85 fold and 6.10 fold in the dissolution rate (K1) of ritonavir tablets respectively. Whereas in combination, HPβCD and Solutol HS15 gave a 16.85 fold increase in the dissolution rate.

The objective of this study was to develop pH independent immediate release (IR) tablet formulation of Glipizide (GPZ) incorporating β-cyclodextrin (β-CD) and a ternary agent produced by high energy air jet milling complexation technique. GPZ (pKa of 5.9) is poorly water soluble (3.9µgm/ml) exhibiting pH dependent solubility (1.1µgm/ml at pH 2.0 and 26.6 µgm/ml at pH 6.8) owing to which it demonstrates dissolution rate limited absorption and bioavailability. Several complexation techniques involving formation of binary and ternary complexes were evaluated for achieving pH independent release of GPZ. Ternary complex involving GPZ:β-CD: Arginine (1:2:1) prepared using high energy air jet milling was found to be most promising in terms of significant enhancement in solubility, further attaining pH independent dissolution. Molecular modelling (MM) was carried out in order to understand the GPZ:β-CD orientation and GPZ group interactions with the cyclodextrin cavities. Molecular modelling suggested interaction of cyclohexyl and methylpyrazinecarboxamido groups of GPZ with the cyclodextrin cavities and favorability of head to tell (HT) orientation due to its minimum interaction energy. XRD and DSC study showed partial amorphization of GPZ. Scanning electron microscopy (SEM) studies revealed formation of new solid phase of ternary complex indicating partial amorphization. Tablets prepared using optimized ternary complex of GPZ showed immediate and pH independent drug release as compared to marketed tablet formulation and plain drug.