Formulation and Evaluation of Dapoxetine HCL Nanoparticle Capsules

The goal of any drug delivery system is to provide a therapeutic amount of drug to the proper site in the body and also to achieve and maintain the desired drug concentration. The λ max of Dapoxetine Hcl as found to be 292 nm in 0.01N Hydrochloric acid and 292nm in Phosphate buffer pH6.8 in 10μg/ml solution. Dapoxetine Hcl is a highly potent SSRI was used as a model drug to develop a controlled release formulation. Dapoxetine Hcl designed to prolong the release increase the drug bioavailability, diminish the side effects of irritating drugs and also reducing the frequency of administration, thereby improving the patient compliance and therapeutic efficacy. The Dapoxetine Hcl obeys the Beers law within the concentration of 5 to 50 μg/ml. Dapoxetine Hcl is having low solubility and short duration elimination half life (1-1.6 hour), the drug displays extensive first pass metabolism. The purpose of this study was to prepare Dapoxetine Hcl nanoparticles for control release of Dapoxetine Hcl to improve the oral bioavailability, enhance the solubility and dissolution rate by decreasing particle size of drug. Infrared spectroscopic studies confirmed that there was no interaction between drug and polymers. The controlled release Dapoxetine Hcl nanoparticles were prepared by Solvent evaporation by using Ethyl cellulose, Chitosan & HPMC K100 M and hyper-cross linked method using Betacyclodextrin and Diphenyl carbonate polymers of 1:1, 1:2, 1:3, 1:4 ratios. The production yield of the formulated controlled release nanoparticles (F1 to F16) in the range of 76.11% to 83.58%. The drug content of the formulated controlled release nanoparticles (F1 to F16) in the range of 82.56 % to 98.20%. The Theoretical loading of the formulated controlled release nanoparticles (F1- F16) in the range of 24.43 % to 64.24%. The entrapment efficiency increased with increasing the concentration of polymers and the formulations containing chitosan nanoparticles F6 (1:2) showed better entrapment (90.94%) among all formulation. The solubility of selected formulation (F6) in 0.2M Phosphate buffer pH6.8 increased when compared to pure drug. Particle size distribution was determined by Malvern zeta size, the size range for produced nanoparticles in the range of 200nm to 400 nm. The polydispersity index of selected nanoparticle formulation (F6) was 0.812 which indicated a narrow range and a homogeneous size distribution of particles. Zeta potential value of Dapoxetine Hcl nanoparticles showed a positive surface charge (+38.1 mV) this is because of more anion on the surface of the particles higher the charge higher is the stability of the nanoparticle. The invitro dissolution study was carried out in 0.01N Hydrochloric acid for 2 hours and phosphate buffer pH 6.8 for 10 hours. The formulations shows controlled release of drug upto 12 hrs and all formulations showed more than 75% of drug release. The release kinetics showed that the formulations were complies with Zero order kinetics followed by diffusion controlled mechanism and Korsemeyar peppas n values were more than 0.4 indicating Nonfickian diffusion. The best formulation F6 was selected based on production yield, entrapment efficiency, solubilization efficiency, particle size, polydispersity index & zeta potential and in-vitro drug release and release kinetics. The best formulation F6 was evaluated by infrared spectroscopy, particle size, polydispersity index & zeta potential, Scanning Electron microscopy, X-ray powder diffraction method (X-PRD) and DSC. Best formulation of nanoparticles shown the extent of drug release was found to be F6 (96.93 %) in 12hrs. SEM studies confirmed the morphology of the nanoparticle formulation. The crystalline state of the nanoparticle formulation was not altered according to the XRPD analysis. The stability studies confirmed that the developed Dapoxetine Hcl nanoparticles are physically and chemically stable and retain their pharmaceutical properties at various temperature and humidity conditions over a period of 2 month. One formulation were selected for invivo studies on mice. The administration of Dapoxetine Hcl loaded nanoparticle significantly inhibit the serotonin reuptake in the synaptic cleft similar trend but the extent of decrease is greater compared to standard drug. The sudden decrease of blood pressure after administration of Dapoxetine Hcl (standard) was due to burst release of drug from nanoparticle which was observed during invitro drug release studies. The anti-depressive activity of Dapoxetine Hcl loaded nanoparticles is lesser than control. Hence, Chitosan NP could be able to maintain the serotonin level over the period of observation(12h). The results can be attributed to the efficacy of formulated Dapoxetine HCL nanoparticles in treating hypertension as well as its role in maintaintaing the therapeutic levels until extended period of time. The Dapoxetine Hcl nanoparticle & selected best formulation (F6) was formulated into capsules using suitable diluents (MCC) by hand filling method. The formulated capsules were analyzed for pre compression and post compression parameter drug content, invitro drug release studies. The pre compression parameters of all the formulations were within the required limit was indicated good flow property, suitable for formulation of the capsules. The post compression parameters such as general appearance, weight variation, uniformity of content and invitro studies of all formulations were within the acceptable limits. FTIR studies of selected best formulation shows that no interaction between the drug and excipients. Dapoxetine Hcl chitosan nanoparticle capsules showed increased drug release profile when compared with Dapoxetine Hcl capsules. CONCLUSION: Hence, it was concluded that nanoparticle a good approach to release the drug in a controlled manner to the targeted site and enhance the solubility and dissolution property of Dapoxetine Hcl by solvent evaporation method for the successful incorporation of Dapoxet ine Hcl with high entrapment efficiency. The solubility studies suggested that the nanoparticle formulations enhanced the bioavailability of Dapoxetine Hcl by improving its solubility and dissolution rate when compared to pure drug. Furthermore, it could be presumed that if the nanometer range of particles were obtained, the bioavailability might be increased. Thus the nanoparticles as controlled release formulations can be useful for delivery of short elimination half life, low bioavailability through orally. Thus nanoparticle drug delivery system provides site specific drug delivery and prolongs dosage interval and thus improving patient compliance. The invivo release studies results indicated the efficacy of formulated Dapoxetine Hcl nanoparticles in treating depression as well as its role in maintaining the therapeutic levels until extended period of time