Formulation and evaluation of Herbal in-situ gel for the Treatment of Rhinosinusitis

Abstract

providers, and they are of great consequence. In a report from the Centers for Disease Control, respiratory tract infections (upper respiratory tract infections, otitis, and lower respiratory tract infections) accounted for 16% of all outpatient visits of patients to physicians. According to the National Ambulatory Medical Care Survey data, sinusitis is the fifth most common diagnosis for which an antibiotic is prescribed. Rhinosinusitis is defined as the inflammation of nasal and paranasal sinus mucosa and is associated with mucosal alterations ranging from inflammatory thickening to gross nasal polyp formation. Etiological factors that causes rhinosinusitis includes systemic host factors and local host factors. Systemic host factors includes: Genetic/congenital conditions, immunodeficiencies/immune suppression, chemotherapy and autoimmune. Local host factors includes: Environmental, infectious, allergy and pollutants. Rhinosinusitis can be diagnosed by clinical history, physical examination and additional techniques like imaging, allergy testing and inflammatory parameters. In-situ gelling system was selected as it provides greater advantage than other dosage forms. By in-situ gelling system the medication can be delivered either locally or systemically in a more controlled and effective way. In-situ gelling dosage form is user-friendly, convenient, painless and offers controlled drug release for a longer period of time. From literature survey we had selected two herbal drugs i.e. Vitex negundo and Cissampelos pareira as they have been proved for their anti-inflammatory action for formulating in-situ gel. These drugs have also been reported for various traditional uses. The present investigation was aimed to formulate anti-inflammatory nasal in-situ gel by incorporating herbal extracts containing various phytoconstituents. Main objective was  To extract the drug,  Optimization and development of the formulation  Evaluation of the optimized formulation.The macroscopic and microscopic studies were performed for Vitex negundo and Cissampelos pareira. The successive phytochemical screening was performed using Pet. ether, Ethyl acetate, Methanolic and Aqueous extracts. Conventional extraction procedure was used for extracting both the drugs. The % yield of Vitex negundo and Cissampelos pareira was found to be 27.4% and 4.35%w/w respectively. The gel was formulated using methanolic extract of both the drugs individually and in the ratio of 1:1 for combination gel. Gellan gum was selected as polymer and was optimized from 0.1-0.5% concentration range. After optimizing, required quantity of the polymer was weighed and dissolved in water in small quantities with continuous stirring on a stirrer until the polymer dispersed homogenously at 90˚C .After cooling to below 40˚C, drug, mannitol, and benzalkonium chloride were added and mixed well. The gel was allowed to equilibrate overnight at 4-8˚C. Various in-vitro parameters such as gelling capacity, gelling time, gel strength, viscosity, pH, transparency and drug permeation study were performed. Ex-vivo drug permeation study were performed on sheep nasal tissue of optimized batch and the concentration of drug was estimated by measuring the absorbance at previously determined λmax of both the drugs using U.V spectrophotometer. In-situ gel containing gellan gum 0.5% was found to have desired gelling capacity for nasal administration. 0.1-0.5% range of gellan gum gel followed pseudoplastic rheology. With increase in rpm the viscosity was found to be decreased. In-vitro drug permeation study of Vitex negundo, Cissampelos pareira and combination gel was found to be 65.34%, 62.43%, 67.76% at 24 hrs resp. Ex-vivo drug permeation study of Vitex negundo, Cissampelos pareira and combination gel was found to be 69.83%, 66.66%, 69.54% at 24 hrs resp. Phenolics and Flavonoids were estimated from the gel. Transparency of the gel decreased from formulation F1 to F5 while the gelling capacity increased from F1 to F5 formulation with gradual increase in the polymer concentration. Current work on in-situ nasal gel has been carried out successfully fulfilling the aim of the study. Using polymer gellan gum we have formulated a satisfactory in-situ gel containing extracts of two different herbal drugs. Rheological study in sol and gel form were performed and from the results we may conclude that 0.5% concentration of gellan gum was sufficient to obtain gel characteristics. The optimized formulation F2 complies all the parameters. In-vitro and ex-vivo release study of batch G1 was found to be more compared to batch G2. By observing the release profiles of the in-vitro and ex-vivo batches, we may conclude that % drug release was found to increase in ex-vivo batches than in-vitro batches As our target population is human subjects the % drug release in ex-vivo diffusion through sheep nasal tissue was found more. So, we may conclude that the same release pattern would be expected in human subjects.