Development of intravaginal rod insert bearing liposomal raloxifene hydrochloride and Leuprolide acetate as a potential carrier for uterine targeting.

OBJECTIVES: This project aimed at the formulation of dual drug entrapped liposomes held as freeze-dried intravaginal rod insert (IVR), to be administered by vaginal route for uterine targeting. METHODS: Liposomes were formulated by dehydration-rehydration method using 3 : 1 molar ratio of1,2-distearoyl-sn-glycero-3-phosphocholine : Cholesterol. Characterization was done for vesicle size, zeta potential, entrapment efficiency, surface morphology and % loading. KEY FINDINGS: Spherical and discrete vesicles of size 354 nm were observed in transmission electron microscopy (TEM) image. The entrapment efficiency of 90.91% and 74.3% w/w was obtained for Raloxifene Hydrochloride (RLX) and Leuprolide acetate (LA) respectively. Drug release was sustained for 6 days. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay results showed that dual drug entrapped liposomal formulation show significant cytotoxicity, as also confirmed by higher apoptosis in cell cycle analysis and apoptosis studies (FACS) analysis. Pharmacodynamic studies in New Zealand white female rabbits revealed that intravaginal administration of RLX-LA entrapped liposomal formulation shows considerable fibroid regression. CONCLUSIONS: Uterine targeting of liposomal RLX-LA suggests its potential to solve the limitations of the presently available therapeutic options.

Formulation and evaluation of liquisolid compacts of itraconazole to enhance its oral bioavailability.

Aim: Formulate and evaluate liquisolid compacts of Itraconazole, a biopharmaceutical classification system class II drug, which has poor bioavailability. Materials & methods: PEG 600 was used as a nonvolatile solvent, Alfacel PH 200 as a carrier and Aerosil 200 as a coating material. The Itraconazole solution upon mixing with a carrier and coating material resulted in a dry powder, which was compressed into tablets. Results & conclusion: The optimized formulation exhibited a significantly higher drug dissolution (90.73% in 90 min) compared with conventional tablets and marketed capsules. The antifungal activity was retained in the formulation. Higher values of Cmax and AUC0-24 of the formulation compared with the plain drug indicated enhancement in oral bioavailability. The formulation was stable at room temperature as well as in accelerated conditions.

99mTc-vinorelbine tartrate loaded spherulites: Lung disposition study in Sprague-Dawley rats by gamma scintigraphy.

Vinorelbine Tartrate (VLB) is the first line chemotherapeutic agent for treatment of Non-Small Cell Lung Cancer, whose non-specific distribution causes unwanted side effects. The aim of the present investigation was to formulate VLB loaded spherulites intended for targeting the lung. Spherulites were composed of Soyabean Phosphatidylcholine (SPC), Cholesterol (Chol), Potassium oleate and Mannitol. Lipid film prepared using SPC, Chol and Potassium oleate, was dispersed in aqueous phase comprising Mannitol and VLB, followed by controlled shearing and extrusion. PEGylated Spherulites were prepared by incorporating 1,2-distearoyl-sn-glycero-3 phosphatidylethanolamine-N-[methoxy poly (ethylene glycol)] (DSPE-PEG 2000) in the lipid phase. Vesicles were characterized for size, entrapment efficiency and drug release. In vitro cell cytotoxicity and apoptosis study were performed on A549 cell line. Radiolabeling of VLB was performed by direct labeling with reduced technetium-99m. Binding affinity of 99mTc- labelled complexes was assessed by diethylenetriaminepenta acetic acid (DTPA) challenge test. Biodistribution study was done in Sprague Dawley rats. Dynamic light scattering and Transmission electron micrographs confirmed that PEGylated and non-PEGylated Spherulites were discrete, spherical and exhibited the size range of 120-130 nm. Non-PEGylated and PEGylated Spherulites had an entrapment efficiency of 95.65% and 94.2% respectively. In vitro drug release study indicated VLB plain drug solution diffused completely within 24 h, however, Non-PEGylated and PEGylated Spherulites showed similar release pattern till 48 h. Results of cell line study showed that cells treated with VLB loaded Spherulites showed more cytotoxicity and underwent high degree of apoptosis at lower concentration compared to the VLB solution. Radiolabeled complex was stable in saline and serum, further, DTPA challenge study ensured the high binding strength. Gamma Scintigraphy displayed that PEGylated Spherulites were localized within lungs at higher concentration than non-PEGylated followed by plain drug.

Biodistribution study of 99mTc-gemcitabine-loaded spherulites in Sprague-Dawley rats by gamma scintigraphy to investigate its lung targeting potential.

Gemcitabine hydrochloride (GCH) is drug of choice for treatment of non-small cell lung cancer. This project aims to formulate GCH-loaded spherulites for lung targeting using soyabean phosphatidylcholine, cholesterol (Chol) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000]. Vesicles were characterised for size, entrapment efficiency, drug release and in vitro cytotoxicity. Radiolabelling of GCH was done using reduced technetium-99 m to study biodistribution in Sprague-Dawley rats. Discrete and spherical, PEGylated and non-PEGylated spherulites with an average size of 200 nm as seen in transmission electron microscopy had an entrapment efficiency of 76.28% and 77.42%, respectively. PEGylated spherulites showed sustained release followed by non-PEGylated and plain drug. GCH spherulites exhibited significantly higher cytotoxicity and apoptosis at reduced concentration than GCH solution. The radiolabelled complex showed high binding and radiolabelling efficiency. Gamma scintigraphy showed that GCH-loaded PEGylated spherulites were able to localise within lungs in higher concentration than non-PEGylated followed by plain drug.

Formulation and evaluation of Itraconazole nanoemulsion for enhanced oral bioavailability.

Itraconazole (ITR), an antifungal agent has poor bioavailability due to low aqueous solubility. The present investigation aimed at development of ITR nanoemulsion to enhance its oral bioavailability. ITR nanoemulsion was prepared using Capmul MCM C8 as oil, Pluronic F68 as co-surfactant and Cremophore EL as surfactant using high speed stirring, followed by probe sonication. Nanoemulsion with average globule size of 100.9 nm and zeta potential of -35.9 ± 1.2 mV was able to penetrate well into the intestinal membrane as confirmed by the laser confocal scanning microscopy and ex vivo intestinal permeability study. Antimycotic study confirmed the efficacy of ITR nanoemulsion. Significantly higher values of pharmacokinetic parameters the formulation than the plain drug and marketed formulation indicated an increase in the bioavailability of ITR. The prepared nanoemulsion was stable at both, refrigerated and room temperature conditions. Nanoemulsion of ITR seems to be a promising formulation for enhancement of its oral bioavailability.

Formulation and evaluation of Itraconazole nanoemulsion for enhanced oral bioavailability.

Itraconazole (ITR), an antifungal agent has poor bioavailability due to low aqueous solubility. The present investigation aimed at development of ITR nanoemulsion to enhance its oral bioavailability. ITR nanoemulsion was prepared using Capmul MCM C8 as oil, Pluronic F68 as co-surfactant and Cremophore EL as surfactant using high speed stirring, followed by probe sonication. Nanoemulsion with average globule size of 100.9 nm and zeta potential of -35.9 ± 1.2 mV was able to penetrate well into the intestinal membrane as confirmed by the laser confocal scanning microscopy and ex vivo intestinal permeability study. Antimycotic study confirmed the efficacy of ITR nanoemulsion. Significantly higher values of pharmacokinetic parameters the formulation than the plain drug and marketed formulation indicated an increase in the bioavailability of ITR. The prepared nanoemulsion was stable at both, refrigerated and room temperature conditions. Nanoemulsion of ITR seems to be a promising formulation for enhancement of its oral bioavailability.