Molecularly pegylated lipid microparticles as a novel sustained-release vaginal delivery system for miconazole nitrate

The purpose of this study was to investigate intravaginal drug delivery system based on biocompatible phytolipids [Softisan® 154 (SF) (hydrogenated palm oil) and super-refined sunseed oil (SO)] and polyethylene glycol (PEG)-4000 for sustained delivery of miconazole nitrate (MN). Lipid matrices (LMs) consisting of optimized 1:9 blend of SO and SF with increasing amounts of PEG-4000 (0, 10, 20, 40 % w/w) were prepared by fusion, characterized by differential scanning calorimetry and employed to formulate MN-loaded solid lipid microparticles (SLMs) by melt-homogenization. In vitro drug permeation of the SLMs was evaluated in simulated vaginal fluid (SVF, pH 4.2). Results of thermal analysis confirmed the amorphous nature of the LMs and also indicated that PEG-4000 was molecularly integrated in non-PEGylated LM yielding more amorphous PEGylated LMs. Drug-loaded PEGylated SLMs based on SO:SF (1:9) and PEG-4000 (40 %w/w) (batch DM) exhibited significantly (p < 0.05) higher in vitro permeation coefficient (1.8022 × 10-4 cm/min) than commercial topical formulation of MN (Fungusol® lotion) (1.3765 x 10-4 cm/min) and pure MN sample (1.1892 x 10-4 cm/min). The developed formulations could be exploited as alternative sustained release intravaginal delivery platform for miconazole nitrate.Keywords: Miconazole nitrate, Softisan® 154, Intravaginal drug delivery, PEGylated solid lipid microparticles, Sustained release, Sunseed oi

Formulation and Evaluation of Glutaraldehyde-Crosslinked Chitosan Microparticles for the Delivery of Ibuprofen

Purpose: Toformulate glutaraldehyde-cross-linked chitosan-based microparticles and evaluate its suitability for the delivery of ibuprofen, a BCS class II drug. Methods: Ibuprofen-loaded chitosan microparticles were prepared by emulsification-cross-linking technique using glutaraldehyde saturated toluene (GST) as the cross-linking agent. The microparticles were characterized with respect to morphology, particle size, microparticle yield and entrapment efficiency. The swelling behaviour of the particles and ibuprofen release were assessed in both simulated gastric fluid (SGF) without pepsin (pH 1.2) and simulated intestinal fluid (SIF) without pancreatin (pH 7.4). Results: Discrete and free-flowing microparticles of size range 100.05 ± 8.82 to 326.70 ± 10.43 μm were obtained. The microparticles had a high yield (69.2 to 99.2 %) and exhibited greater water sorption capacity in SIF (122.2 %) than in SGF (60 %). Furthermore, the microparticles cross-linked with 10 ml of GST entrapped the highest amount of drug (23.32 ± 0.97 %) while those cross-linked with 25 ml GST had the highest yield of the microparticles (99.19 % ), and highest water sorption in SIF (122.2 %). Up to 93.6 % of the entrapped drug was released in SIF from microparticles cross-linked with 25 ml of GST. Drug release from microparticles cross-linked with 20 and 30 ml each of GST showed a biphasic pattern. Conclusions: Entrapment of ibuprofen in glutaraldehyde-cross-linked chitosan microparticles can be exploited to target and control the release of the drug and possibly reduce its gastro-erosive side effects

Physicochemical and safety characteristics of novel microstructured lipid-based drug delivery system encapsulating miconazole nitrate

This study was designed to investigate an intravaginal drug delivery system based on biocompatible phytolipids [Softisan® 154 (SF) (hydrogenated palm oil) and super-refined sunseed oil (SO)] and polyethylene glycol (PEG)-4000 for improved physicochemical performance and safe delivery of miconazole nitrate (MN). Lipid matrices (LMs) consisting of optimized 1:9 blend of SO and SF with increasing amounts of PEG-4000 (0, 10, 20, 40 % w/w) were employed to formulate MN-loaded solid lipid microparticles (SLMs) by melt-homogenization. The SLMs were evaluated in terms of encapsulation efficiency (EE), loading capacity (LC), particle size, morphology, tolerability in female rabbits and stability. Results showed that SLMs based on SO:SF (1:9) and PEG-4000 (40 %w/w) gave highest EE (88.05%) and LC (25.00 g of MN per 100 g of lipid). This optimized formulation (DM) had the least particle size, mostly spherical microparticles. Moreover, the formulation was stable and histopathologically safe. This study has shown that the developed microstructured lipid-based formulation could be employed for improved physicochemical performance and safe intravaginal delivery of miconazole nitrate.Keywords: Miconazole nitrate, Softisan® 154, Intravaginal drug delivery, Physicochemical performance, vaginal tolerance test (VTT), Biocompatible phytolipid