Sree Ranjani, P (2021) Design and Development of Proliposomal Dry Powder Inhalation for Pulmonary Delivery of Antihypertensive Drug. Masters thesis, C. L. Baid Metha College of Pharmacy, Chennai.
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Abstract
The objective of the present study was to Design and Development of Proliposomal Dry Powder Inhalation for Pulmonary Delivery of Antihypertensive Drug. The oral recommended dose for AT tablet is between 25 and 100 mg, twice daily. Conventional oral administration usually results in erratic drug concentrations in plasma because of Atenolol lower permeability, leading to dose dumping and reduction in the pharmacological effect or development of undesirable side effects. Hence, considering these disadvantages inhalatory administration of atenolol is considered one of the main alternative non-invasive drug delivery route and it is particularly interesting for cardiac targeting. This is because during absorption, drugs are predominantly first transported to the heart via the pulmonary vein. Pulmonary epithelium is relatively extensive and widely vascularised. In addition, there is little presence of efflux transporters, which favours drug absorption. So preparing a targeted drug delivery system in terms of atenolol proliposomes could be an interesting alternative option to directly reach the cardiac tissue and decrease systemic exposure. Via this route, onset of action can be relatively fast, metabolic enzymes levels are lower compared to hepatic ones. Hence the drug, even with different physicochemical properties can be absorbed. In addition, pulmonary administration route exerts may advantages as alveolar membrane is extremely thin and highly permeable so the pulmonary absorption of different APIs also possible. Hence Atenolol proliposomes were prepared and optimized using Box-Behnken Design is justifiable. Atenolol proliposomes were prepared by using various concentration ratio of SPC (2, 4 & 6g) and Cholesterol (2, 4 & 6g) and stirring speed (170, 220 & 270 rpm) with response of particle size and percent drug permeated. Based on the characterization of drug permeability and particle size of the atenolol proliposomes, the optimized formulation was selected. The data collected from the invitro drug permeability, were then analysed using RSM to determine the effect of each parameter and the effects of various parameters involved were then interpreted. The best composite of SPC and cholesterol was selected from the various ratios. The ratio of 4 g of SPC, 4g of cholesterol and stirring speed 220 rpm (F13) was selected. The in-vitro permeability of optimized formulation shows 93.78% for 12 hours. the drug release kinetics, data obtained from In-Vitro drug release studies are plotted in various kinetic models. The curve fitting results of the rate of permeation of the designed formulations gave an idea of the mechanism of drug release. Based on the “n” value of 0.6299 the drug release was found to follow non-Fickian diffusion, which indicated both diffusion and swelling mechanism. Also, the drug release mechanism was best explained by Higuchi, as the plots showed the highest linearity (r2 = 0.9919), as the drug release was best fitted in Higuchi. The optimized formulation showed particle size of 683nm. The PDI value of atenolol proliposomes was found to be 0.903. The poly dispersity index less than <1 indicates good uniform distribution of particles. The results obtained from the in vivo pharmacodynamic study shows that administration of optimized atenolol proliposome results in gradual decrease of BP, they decreased the BP significantly at the first hour and the effect continued for 12 hrs. The in-vivo pharmacokinetics study states that oral administration of pure Atenolol shows 3.75hrs MRT, whereas in the case of optimized formulation it shows 6.4hrs. The plasma dug concentration was maintained till 12 hrs, when given as proliposomes, hence the objective of the present study confirms the justification of delivering AT in proliposomal form through nebulization. Hence the dosing frequency can be reduced and bioavailability of the drug is increased as compared to oral administration. From the above result, it can be concluded that, atenolol proliposomes have promising drug delivery attributes for antihypertension.
| Item Type: | Thesis (Masters) |
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| Additional Information: | 261910014 |
| Uncontrolled Keywords: | Design, Development, Proliposomal Dry Powder Inhalation, Pulmonary Delivery, Antihypertensive Drug. |
| Subjects: | PHARMACY > Pharmaceutics |
| Depositing User: | Subramani R |
| Date Deposited: | 01 Nov 2022 03:09 |
| Last Modified: | 01 Nov 2022 03:09 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/20857 |
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