Plain Drug Solution Research Articles

Enhanced Transdermal Delivery of Acyclovir Sodium via Elastic Liposomes

The elastic liposomes bearing acyclovir sodium were prepared for its enhanced transdermal delivery by conventional rotary evaporation method and characterized for various parameters such as vesicle shape and surface morphology, size and size distribution, entrapment efficiency, elasticity, polydispersity index, turbidity and in vitro release pattern. Permeability studies of acyclovir sodium incorporated in elastic liposomes were performed across artificial membranes and rat skin. Skin permeation potential of the developed formulation was assessed using confocal laser scanning microscopy, that revealed an enhanced permeation of the formulation to the deeper layers of the skin (up to 160 μm) following channel like pathways. Skin permeation profile of elastic liposomal formulation bearing acyclovir sodium was observed and the investigations revealed an enhanced transdermal flux (6.21 ± 1.8 μg/cm2/hr) and decreased lag time (0.6 hr) for acyclovir sodium. The obtained flux was nearly 2.0 and 6.3 times higher than conventional liposomal formulation bearing acyclovir sodium and plain drug solution, respectively (p < 0.01). The elastic liposomal formulation for transdermal delivery of acyclovir sodium provides better transdermal flux, higher entrapment efficiency, ability as a self-penetration enhancer and effectiveness for transdermal delivery as compared with conventional liposomes. In vivo studies showed that on transdermal application of elastic liposomes, the concentration of acyclovir sodium in plasma was found to be 105 ± 9.4 ng/ml after 24 hr which is about 4.2 times compared with conventional liposomes. Thus it is concluded that the elastic liposomes may be promising vehicles for the transdermal delivery of acyclovir sodium.

Targeted delivery of 5-ASA to colon using chitosan hydrogel microspheres

The present study is aimed at developing hydrogel microspheres of chitosan grafted with vinyl polymers for the controlled release of 5-ASA to the colon in rodents. The graft copolymer of chitosan with acrylamide was synthesized and used to prepare microspheres by water-in-oil (w/o) emulsification method (CHI-g-AAm). The microspheres were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, dynamic swelling and in vitro drug release. The prepared microspheres were spherical with smooth surfaces. The in vitro 5-ASA release from chitosan hydrogel microspheres exhibited significantly higher drug release in simulated colonic fluid containing caecal and colonic content than that in the simulated stomach and small intestinal fluid. Drug release in simulated fluids such as simulated intestinal fluid (SIF-pH 7.0), was found to be 84.4 ± 1.8% and 91.1 ± 1.3% in the presence of 5 and 10% rat caecal content (RCC), respectively, at the end of 8 h. The drug loaded microspheres were also studied for the healing of 2,4,6-trinitrobenzene sulfonic acid sodium salt (TNBS)-induced colitis in rats. The colonic injury and inflammation were assessed by measuring the myeloperoxidase (MPO) activity, colon wet weight/body weight (C/B) ratio and the damage score, respectively. Grafted chitosan microspheres bearing 5-ASA exhibited better therapeutic effects as evaluated by the MPO activities, C/B ratio and the damage score in comparison to 5ASA plain drug solution in oral administration.

Development of Liposomal Systems of Finasteride for Topical Applications: Design, Characterization, and In Vitro Evaluation

Finasteride (FNS) is a “drug of choice” for benign prostate hypertrophy and prostate cancer. The drug has also been reported to be useful orally in the treatment of some difficult-to-treat androgen-dependent skin disorders, such as seborrhea, acne, hirsutism, and androgenetic alopecia. However, the ideal route for its administration (i.e., topical) remains unexplored. This has logically suggested the search for strategic formulation approaches to make the drug effective on topical applications, hitherto unexplored. The present study targets the encasement of drug molecules in the interiors of vesicular compartments (liposomes) made up of hydrogenated phospholipids, as an attempt toward the development of a trans-epidermal therapeutic system of FNS. Multilamellar drug-loaded liposomes were prepared by thin-film hydration with sonication method and optimized with respect to drug payload, entrapment efficiency, and size by formulating different vesicular compositions under different process conditions. The vesicular systems consisting of saturated phospholipid (100 mg), cholesterol (50 mg), and FNS (5 mg) showed highest drug payload (2.9 mg/100 mg of total lipids), and drug entrapment efficiency (88.6%). Mean (± SD) vesicle size of the prepared liposomes was found to be 3.66 ± 1.6 μm. Significantly higher skin permeation of FNS through excised abdominal mice skin of FNS was achieved from the liposomal formulations vis-à-vis corresponding solution and conventional gels. Liposomal FNS formulations also showed more than fivefold higher deposition of drug in skin than the corresponding plain drug solution and conventional gel. Stability studies indicated that the liposomal formulations were quite stable in the refrigerated conditions for 2 months with negligible drug leakage or vesicle size alteration during the storage period. Results of the current studies with FNS-loaded vesicular systems project the high plausibility of a topical liposomal formulation for effective localized delivery of Finasteride.

Elastic Liposomes Mediated Transdermal Deliveryof an Anti-Hypertensive Agent: Propranolol Hydrochloride

One major problem encountered in transdermal drug delivery is the low permeability of drugs through the skin barrier. In the present investigation ultradeformable lipid vesicles, that is, elastic liposomes were prepared incorporating propranolol hydrochloride for enhanced transdermal delivery. Elastic liposomes bearing propranolol hydrochloride were prepared by conventional rotary evaporation method and characterized for various parameters including vesicles shape and surface morphology, size and size distribution, entrapment efficiency, elasticity, turbidity, and in vitro drug release. In vitro flux, enhancement ratio (ER), and release pattern of propranolol hydrochloride were calculated for transdermal delivery. In vivo study conducted on male albino rats (Sprague Dawley) was also taken as a measure of performance of elastic liposomal, liposomal, and plain drug solution. The better permeation through the skin was confirmed by confocal laser scanning microscopy (CLSM). Results indicate that the elastic liposomal formulation for transdermal delivery of propranolol hydrochloride provides better transdermal flux, higher entrapment efficiency, ability as a self-penetration enhancer and effectiveness for transdermal delivery as compared to liposomes.

Transdermal delivery of a pineal hormone: Melatonin via elastic liposomes

Melatonin (MT) is a good candidate for transdermal delivery considering its short biological half-life, low molecular weight and a variable oral absorption. The objective of this work was to develop a novel formulation of melatonin for its efficient transdermal delivery. Melatonin loaded elastic liposomal formulation was prepared, characterized and the effect of this developed formulation on the in vitro permeation of melatonin across human cadaver skin was investigated, using a locally fabricated Franz diffusion cell. Skin permeation potential of the developed formulation was assessed using confocal laser scanning microscopy (CLSM), which revealed an enhanced permeation of the formulation to the deeper layers of the skin (up to 180 μm) following channel like pathways. Skin permeation profile of melatonin through elastic liposomal formulations was observed and the investigations revealed an enhanced transdermal flux (51.2±2.21 μg/cm 2/h), decreased lag time (1.1 h) and an optimum permeability coefficient (15.06±0.52 cm/h) for melatonin. The obtained flux was nearly 5 and 12.3 times higher than conventional liposomal and plain drug solution, respectively ( P<0.005). Our result suggests the feasibility of elastic liposomal system for transdermal delivery of melatonin thereby eliminating the limitations of long lag time and poor skin permeation associated with the drug.

Proultraflexible lipid vesicles for effective transdermal delivery of levonorgestrel: Development, characterization, and performance evaluation

The present investigation aimed at formulation, performance evaluation, and stability studies of new vesicular drug carrier system protransfersomes for transdermal delivery of the contraceptive agent, levonorgestrel. Protransfersome gel (PTG) formulations of levonorgestrel were prepared and characterized for vesicle shape, size, entrapment efficiency, turbidity, and drug permeation across rat skin and were evaluated for their stability. The system was evaluated in vivo for biological assay of progestational activity including endometrial assay, inhibition of the formation of corpora lutea, and weight gain of uterus. The effects of different formulation variables (type of alcohol, type and concentration of surfactant) on transdermal permeability profile were assessed. The optimized PTG formulation showed enhanced in vitro skin permeation flux of 15.82 +/- 0.37 microg/cm2/hr as compared to 0.032 +/- 0.01 microg/cm2/hr for plain drug solution. PTG also showed good stability and after 2 months of storage there was no change in liquid crystalline nature, drug content, and other characteristic parameters. The peak plasma concentration of levonorgestrel (0.139 +/- 0.05 microg/mL) was achieved within 4 hours and maintained until 48 hours by a single topical application of optimized PTG formulation. In vivo performance of the PTG formulation showed increase in the therapeutic efficacy of drug. Results indicated that the optimized protransfersomal formulation of levonorgestrel had better skin permeation potential, sustained release characteristic, and better stability than proliposomal formulation.

Aerosolized liposome-based delivery of amphotericin B to alveolar macrophages

The present study was aimed at preparation, characterization, and performance evaluation of amphotericin B (Amp B)-loaded aerosolized liposomes for their selective presentation to lungs (alveolar macrophages), that being the densest site of Aspergillosis infection. Egg phosphatidylcholine (PC)- and cholesterol (Chol)-based liposomes were modified by coating them with alveolar macrophage-specific ligands ( O-palmitoyl mannan, OPM, and O-polmitoyl pullulan, OPP). The prepared formulations were characterized in vitro for vesicle morphology, mean vesicle size, vesicle size distribution and percent drug entrapment. Pressurized packed systems based on preformed liposomal formulations in chlorofluorocarbon aerosol propellants were prepared. In vitro airways penetration efficiency of the liposomal aerosols was determined by percent dose reaching the peripheral airways, it was recorded 1.4–1.6 times lower as compared to plain drug solution-based aerosol. In vivo tissue distribution studies on albino rats suggested the preferential accumulation of OPM- and OPP-coated formulations in the lung macrophages. Higher lung drug concentration was recorded in case of ligand-anchored liposomal aerosols as compared to plain drug solution and plain liposome-based aerosols. The drug was estimated in the lung in high concentration even after 24 h. The drug-localization index calculated after 6 h was nearly 1.42-, 4.47-, and 4.16-fold, respectively, for plain, OPM-, and OPP-coated liposomal aerosols as compared to plain drug solution-based aerosols. These results suggest that the ligand anchored liposomal aerosols are not only effective in rapid attainment of high-drug concentration in lungs with high population of alveolar macrophages but also maintain the same over prolonged period of time. The significance of targeting potential of the developed systems was established.

Preparation and characterization of microencapsulated gelospheres for controlled oral theophylline delivery

Microencapsulated gelospheres were prepared using the water swellable polymers, poly(vinyl alcohol) and polyacrylamide in which the drug was embedded. Polymeric coating was formed by interfacial polymerization using 1,6 hexamine and sebacoyl chloride. The size, shape, in vitro release, kinetics and in vivo efficiency of the formulation were determined. The shape was found to be spherical with a size range below 100 microm. The per cent drug loaded was found to be higher in the case of gelospheres prepared with polyacrylamide than those prepared with poly(vinyl alcohol). The release rate was found to be near zero order. The AUC was found to be higher in the case of polyacrylamide and polyvinyl alcohol gelospheres as compared to plain drug solution.

Poly(phthaloyl-l-lysine)-coated multilamellar vesicles for controlled drug delivery: in vitro and in vivo performance evaluation

Nonionic surfactant vesicles were prepared using Span 60, cholesterol and dicetyl phosphate. The prepared multilamellar vesicles (MLVs) were coated by interfacial polymerization technique using p-phthaloyl dichloride and l-lysine. The formation of the polymeric coat was confirmed by optical microscopic and transmission electron microscopic studies. The prepared, plain and polymer-coated MLVs were studied for their size, shape, encapsulation efficiency, in vitro release profile and effect of osmotic shock on vesicle. The results observed showed that the polymer-coated MLVs were stable under various osmotic conditions. In vivo studies were carried out on albino rats. The half-life and area under curve were found to be high in the case of polymer-coated MLVs as compared to plain MLVs and plain drug solution. In vivo studies using inflammed rat model also indicated that the polymer-coated MLVs were more stable and could release the drug in a controlled fashion as compared to plain MLVs.