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Lipid-based self-nanoemulsifying drug delivery system was explored to improve the oral bioavailability and target specificity of mebendazole for treatment of lymphatic worm infestations. Ternary phase diagrams were constructed to select suitable oil-surfactant mixture. Liquid self-nanoemulsifying drug delivery system consisting of Capmul MCM L8, Chromophore RH40 and tocopherol polyethylene glycol succinates a pre-concentrate was systematically optimized using 32 full factorial designs. β-cyclodextrin-based nanosponges were used to prepare solid self-nanoemulsifying drug delivery system. Characterization of liquid self-nanoemulsifying drug delivery system was carried out using percent transmission, globule size, zeta potential, polydispersity index and drug content. Globule size in the range of 50-90 nm and zeta potential of --5 to --12 mV was obtained, which co-related well with percent transmission. Powder X-ray diffraction, differential scanning calorimetry and scanning electron microscope of solid self-nanoemulsifying drug delivery system indicated the presence of mebendazole as a molecular dispersion. Ex vivo studies showed nearly five-fold increase in the flux. In vivo studies showed two-fold increase in bioavailability. Significant enhancement in drug dissolution and saturation solubility from solid self-nanoemulsifying drug delivery system resulted in an increase in the bioavailability. Besides this, greater surface area, improved release, P-gp modulation potential of excipients and lymphatic bypass via Peyer's patches protected drug from hepatic first pass metabolism all of which would contribute to the observed improved bioavailability. Lymphatic transport of drug could achieve target specificity in lymphatic filariasis. [ABSTRACT FROM AUTHOR]

Efavirenz is a non-nucleoside reverse transcriptase inhibitor which is chronically prescribed for HIV patients. However, it exhibits solubility-limited bioavailability. Aim of this work was to enhance the solubility and dissolution of the Biopharmaceutical Classification System (BCS) class II drug efavirenz, using beta-cyclodextrin-based nanosponges. Nanosponges have high drug loading capacity and are effective for solubility enhancement. Beta-cyclodextrin was crosslinked with carbonates in different ratios to prepare nanosponges. The nanosponges were loaded with efavirenz by solvent evaporation method and the nanosponge with higher drug loading capacity was selected for further studies. Binary and ternary complexes with EFA, NS, and PVP K30 were prepared and characterized by phase solubility, solution state interaction, saturation solubility, in vitro dissolution, and in vivo pharmacokinetics. Spectral analysis by Fourier transform infrared spectroscopy, powder X-ray diffraction, differential scanning calorimetry, and field emission scanning electron microscopy was performed. Results obtained from spectral characterization confirmed inclusion complexation. Stability constant for ternary complex was found to be 1997 lit/mole, which indicates stable complex formation. The saturation solubility was found to be 17-fold higher with ternary complex in distilled water and about 4-fold in simulated gastric fluid. In vitro dissolution was improved 3 folds with ternary complex. Ternary nanosponge complexes were found to have 2-fold increase in oral bioavailability of efavirenz as compared to plain drug.

Parkinson's disease is a degenerative disorder of the central nervous system (CNS). The most obvious symptoms are movement-related such as shaking, rigidity, slowness of movement and difficulty with walking, rigid muscular movements and difficulty in chewing and swallowing especially solid dosage forms. Ropinirole is an anti-Parkinson drug that has low oral bioavailability which is primarily due to first-pass metabolism. The objective of proposed work was to increase bioavailability of ropinirole and avoid patient discomfort by formulating thermoreversible in situ nasal gel. Thermoreversible nasal gels were prepared by cold method using Pluronic F-127 and hydroxy methyl propyl cellulose (HPMC K4M) as gelling agents. Formulations were evaluated for various parameters such as drug content, pH, gelling time, gelling temperature, gel strength, mucoadhesive force, ex vivo diffusion, histological studies and in vivo bioavailability. Formulations displayed gelation at nasal temperature and the gelation time was found to be less than mucociliary clearance time. The nasal residence time was seen to be increased due to mucoadhesion and increased gel strength. The nasal gel formulations showed ex vivo drug release between 56-100% in 5 h. Histological study of sheep nasal mucosa revealed that the gel had a protective effect on the mucosa unlike plain ropinirole which showed evidence of moderate cellular damage. A fivefold increase in bioavailability in brain was observed on nasal administration as compared to IV route. Thermoreversible in situ nasal gel was found to a promising drug delivery for Parkinsonian patients.