FORMULATION AND EVALUTION OF MUCOADHESIVE THERMOSENSITIVE PLURONIC LECITHIN ORGANOGEL OF CLOTRIMAZOLE FOR VAGINAL CANDIDASIS
Amit Jain*, Sandesh Jain, A.G. Hariharan, C.K. Sudhakar, Sanjay Jain
Department of Pharmaceutics,
Smriti College of pharmaceutical education, Indore-452001,
Madhya Pradesh, India
The present investigation deals with development of mucoadhesive thermosensitive pluronic lecithin organogel of clotrimazole for vaginal candidasis. To develop more effective treatment for vaginal candidasis, clotrimazole (CT) was formulated as pluronic lecithin organogels (PLOs). Several PLOs formulations composed of clotrimazole (1%) using the thermosensitive polymer Pluronic® F127, Soya lecithin with the mucoadhesive polymer Carbopol 934. Spreadibility, rheological behavior, drug content (%), mucoadhesive force, gelling capacity and in-vitro release profiles of the different formulations were determined. In vitro, sustained release of CT from PLOs was observed. In vivo antifungal activity of CT, tested against Candida albicans vaginitis in agar plate, was significantly prolonged after vaginal delivery using PLOs. These results indicate that CT-containing vaginal PLOs safe, convenient, and effective treatment of vaginal candidasis with reduced dosing interval.
Reference Id: PHARMATUTOR-ART-1297
Genital tract infections, which are among the most frequent gynecological diseases. It has been reported that 30–50% of vaginitis episodes are due to Candida infection and that two-thirds of all women experience acute episodes of vaginal candidasis at least once during their life time . For the treatment of vaginitis, topical antifungal chemotherapy has been favored owing to the toxicity of antifungal drugs after systemic administration.
For vaginal delivery systems of antifungal agents to be more effective, they need to reside at the sitesof infection for a prolonged period. In additionconvenience of dosing methods is an important factor in the design of vaginal application forms. Of vaginal dosage forms, patients are known to better tolerate gels than inserts or ointments . However, the direct application of gels onto the infected sites of the vagina might be difficult as well as inconvenient. Moreover, conventional gels do not remain for long at the site of application, leading to frequent dosing with antifungal agents.Vaginal candidasis, treated commonly with imidazole derivative antifungal agents such as clotrimazole since these drugs are locally active with no major side effects [4, 5].
Current vaginal delivery systems include creams, foams, gels, tablets, pessaries and irrigations, which are limited use because of less residence time at the genitourinary tract: they are removed rather rapidly by the self-cleansing action of the vaginal tract [6, 7]. Moreover, the physiological conditions imposed by the protective mechanism of the genital tract, limiting the residence time and thus impairing the therapeutic efficacy of the drug, make multiple and frequent administration necessary for treatment. Patient compliance when administering the dosage forms and following the repeated-dose therapeutic regimen is an important challenge in vaginal drug delivery. Patients are generally reported to tolerate organogels better than other dosage forms .
PLOs are clear, viscoelastic, biocompatible, and isotropic gels composed of phospholipids (lecithin), appropriate organic solvent, and a polar solvent[9,10].Ease of preparation and scale-up, easier quality monitoring, thermodynamic stability, enhanced topical performance along with biocompatibility, safety upon applications for prolonged period, and unique property, that it can incorporate both hydrophilic and lipophilic drugsmake the organogels a vehicle of choice for topical drug delivery.
Mucoadhesive vaginal organogels containing Carbopol enhancing the adhesion of the administered dosage form to the mucosal tissue have been added to thermosensitive organogels prepared with Pluronic f127[11-15]. Different techniques are adopted in drug delivery with thermosensitive organogels, including dispersing the drug in the organogel with a concentration higher than its solubility value and dispersing drug-loaded nanoparticles, liposomes, and drug: cyclodextrin complexes [16-20].
The objective of this study was to design a vaginal organogel formulation with thermosensitive and mucoadhesive properties to ensure longer residence at the infection site, providing a favorable release profile for the antifungal drug clotrimazole.
Materials and methods
CT was provided as gift sample by Apex Pharmaceuticals Pvt. Ltd. Ahmedabad. Pluronic F127 were supplied by Sigma chemicals and soya lecithin from Himedia laboratories (Mumbai). All other chemicals were of reagent grade and used further without purification.
Preparation of formulations
PLOs were prepared by using the cold method [20, 21]. Aqueous phase were prepared by dispersing Carbopol 934 in citrate-phosphate buffer (0.1 M, pH 4.0) at 4 ?C with gentle mixing. Pluronic F-127was then added to carbopol 934 solution and allowed to dissolve overnight at 4 ?C. Oil phase was prepared by dissolving soya lecithin and sorbic acid in appropriate quantity of isopropyl myristate. The mixture was kept overnight at 4ºC in refrigerator for complete dissolution of its constituents. CT was initially dissolved in the mixture of ethanol and polyethylene glycol (PEG) 400 (3:5), and mixed with lecithin isopropyl myristate solution., Finally aqueous phase (70%) was slowly added in oil phase (30%) in with stirring at 400 rpm using mechanical stirrer.
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