Fabrication and Evaluation of Tamsulosin and Dutasteride co-loaded Transferosomes for Treatment of Benign Prostatic Hyperplasia

Abstract

Benign prostatic hyperplasia (BPH) also known as prostate gland enlargement is the fourth most commonly diagnosed medical condition which effect more than half of the Men population at the age greater than 50 years. BPH is a pathological condition characterized by increase in the tissue size due to spread of prostrate stromal cells. Most effective drugs used for the treatment of BPH are Tamsulosin (TAM) and Dutasteride (DUTA) in combination. TAM & DUTA belong to class of α- Blockers and 5 α-Reductase Inhibitors respectively. The problems associated with the oral use of these drugs are Extensive hepatic metabolism by cytochrome P3A4 and P2D6, undesirable side effects due to variation in plasma level, Absorption effected by food in the stomach, Poor aqueous solubility (0.038 ng/mL at 25 °C) and low Bioavailability (40-60%) of Dutasteride. To address the stated problems TAM & DUTA were loaded in Transferosomes and delivered transdermally. Transdermal route was selected to protect the drugs from hepatic First pass effect, also to avoid GIT related side effects associated with Oral administration. The rationale of using Transferosomes for this study is the ultradeformable nature, Biocompatibility and the ability to encapsulate both drugs of different nature. Transferosomes were prepared by Thin film hydration method and the key materials used were Drugs (TAM & DU), Phospholipids (Phospholipon 90G) and Tween-80 (Edge Activator). Both the Drugs, Lipid and Edge activator were optimized quantitatively using Design Expert version 12, Box Behnken model. Response variables were Particle size, Zeta potential and Entrapment efficiency. The resulted formulation was evaluated for physicochemical characteristics like mean vesicle size, Poly dispersity index and zeta potential. Entrapment Efficiency was determined using indirect centrifugation method. Morphological investigation was performed using Transmission electron microscope (TEM Analysis). FTIR analysis were conducted to ensure the lack of Interactions between formulation ingredients. Ex-vivo permeation and drug deposition studies were performed Using Franz diffusion cell apparatus. Drug release studies were performed to confirm the release of drugs at blood PH by using Dialysis Method. V The results indicated that the optimized formulation showed 71% Entrapment efficiency for TAM and 76% EE for DUTA, vesicle size about 174nm and Zeta potential of -17mv. Moreover, the Transferosomal formulation show sustain drug release as compare to raw drug suspension, drug release followed more sustained pattern when transferosomal formulation was loaded into HPMC based Carbopol gel. Due to ultra-deformable nature of Transferosomes the transdermal permeation was quite enhanced when compared to raw drug suspension. Transferosomes appeared spherical and uniform in TEM Analysis. Overall, it can be concluded that Transferosome had proven to be an efficient formulation for transdermal drug delivery of more than one drugs