Cyclodextrin based drug delivery system of protease inhibitor - Nelfinavir Mesylate

The purpose of present investigation was to understand the interactions involved in complexation of Nelfinavir Mesylate (NM)-a protease inhibitor, used in the treatment of HIV/AIDS with Beta-cyclodextrin (beta-CD) and its subsequent effect on its absorption properties and bioavailability. Milling method was used for complexation. The inclusion complexes were characterized by 2D NOESY NMR and ITC studies. The feasibility of findings was further confirmed by using Cerius(2) software of Tripos Inc. using Silicon Graphics O-2. Pharmacokinetic studies were carried out in rabbits and data was treated by Student's t Test. 2D NOESY NMR studies showed very intricate behavior showing interactions amongst drug and beta-CD molecule as well as amongst beta-CD-beta-CD molecules. This fact of formation of molecular aggregates was further confirmed by ITC studies. Computer simulation studies further supported the finding of forming shallow complex. The percent relative bioavailability of complex at the dose of 400 mg/kg in rabbits was 185.37 as compared to the plain NM at 400 mg/kg dose. The studies were conducted at low dose of 200 mg/kg of drug in the form of complex in rabbit does not show statistically significant difference in AUC, T (1/2) and Kel. as compared to plain drug at 400 mg/kg of rabbit

<span style="font-size:11.0pt;font-family: "Times New Roman";mso-fareast-font-family:"Times New Roman";mso-bidi-font-family: Mangal;mso-ansi-language:EN-GB;mso-fareast-language:EN-US;mso-bidi-language: HI" lang="EN-GB">Polymeric nanoparticle formulation of Octapeptide (NP-OP): <i style="mso-bidi-font-style:normal">In vitro</i> release and <i style="mso-bidi-font-style:normal">in vivo</i> effect in common marmosets, <i style="mso-bidi-font-style:normal">Callithrix jacchus </i>Linn.</span>

1055-1062Octapeptide (OP)/FSH-Receptor Binding Inhibitor-8 (FRBI-8), is a synthetic peptide corresponding to N-terminal sequence of purified fraction of Follicle Stimulating Hormone Binding-Inhibitor (FSHBI), isolated earlier from human ovarian follicular-fluid. In order to avoid the repeated drug-administration, OP-loaded, polymeric polylactide (PLA) nanoparticle formulation (NP-OP), was developed using multiple-emulsion technique. This yielded an average particle size of 120 nm with 70% encapsulation-efficiency. In vitro release profile of NP-OP showed sustained release of OP for 21 days. In vivo anti-fertility studies were conducted in marmosets. Results indicated that control animals conceived in the same cycle while two of three treated animals failed to conceive in treatment cycle. The <i style="mso-bidi-font-style: normal">in vivo studies thus corroborate with in vitro release of OP, demonstrating its anti-fertility activity in 66% of animals. </span

Cyclodextrin-Based Nanosponges for Delivery of Resveratrol: In Vitro Characterisation, Stability, Cytotoxicity and Permeation Study

The aim of this work was to increase the solubility, stability and permeation of resveratrol by complexation with cyclodextrin-based nanosponges (NS). Nanosponges are recently developed hyper-cross-linked cyclodextrin polymers nanostructured to form three-dimensional networks; they are obtained by reacting cyclodextrin with a cross-linker such as carbonyldiimidazole. They have been used to increase the solubility and stability of poorly soluble actives. This study aimed at formulating complexes of resveratrol with β-cyclodextrin nanosponges in different weight ratios. DSC, FTIR and X-ray powder diffraction (XRPD) studies confirmed the interaction of resveratrol with NS. XRPD showed that the crystallinity of resveratrol decrease after encapsulation. The particle sizes of resveratrol-loaded NS are in between 400 to 500 nm with low polydispersity indices. Zeta potential is sufficiently high to obtain a stable colloidal nanosuspension. TEM measurement also revealed a particle size around 400 nm for NS complexes. The in vitro release and stability of resveratrol complex were increased compared with plain drug. Cytotoxic studies on HCPC-I cell showed that resveratrol formulations were more cytotoxic than plain resveratrol. The permeation study indicates that the resveratrol NS formulation showed good permeation in pigskin. The accumulation study in rabbit mucosa showed better accumulation of resveratrol NS formulation than plain drug. These results signify that resveratrol NS formulation can be used for buccal delivery and topical application

Solubility enhancement of cox-2 inhibitors using various solvent systems

This study examined the solubility enhancement of 4 cox-2 inhibitors, celecoxib, rofecoxib, meloxicam, and nimesulide, using a series of pure solvents and solvent mixtures. Water, alcohols, glycols, glycerol, and polyethylene glycol 400 (PEG 400) were used as solvents and water-ethanol, glycerol-ethanol, and polyethylene glycol-ethanol were used as mixed-solvent systems. A pH-solubility profile of drugs was obtained in the pH range 7.0 to 10.9 using 0.05M glycine-sodium hydroxide buffer solutions. Lower alcohols, higher glycols, and PEG 400 were found to be good solvents for these drugs. The aqueous solubility of celecoxib, rofecoxib, and nimesulide could be enhanced significantly by using ethanol as the second solvent. Among the mixed-solvent systems, PEG 400-ethanol system had highest solubilization potential. In the case of meloxicam and nimesulide, solubility increased significantly with increase in pH value. Physico-chemical properties of the solvent such as polarity, intermolecular interactions, and the ability of the solvent to form a hydrogen bond with the drug molecules were found to be the major factors involved in the dissolution of drugs by pure solvents. The greater the difference in the polarity of the 2 solvents in a given mixed solvent, the greater was the solubilization power. However, in a given mixed-solvent system, the solubilization power could not be related to the polarity of the drugs. Significance of the solubility data in relation to the development of formulations has also been discussed in this study