Prasanna, G (2021) Formulation Development and Evaluation of Cilnidipine Nanosuspension for the treatment of Hypertension using Anti-Solvent Precipitation and Ultrasonication Method. Masters thesis, College of Pharmacy, Madras Medical College, Chennai.
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Abstract
The present study was aimed to develop a novel method for improving the oral bioavailability by enhancing the solubility of poorly water drug cilnidipine and to improve the patient compliance. Cilnidipine is a poorly water soluble drug with a short half life, thus selected for developing Nanosuspension formulation with improved in the solubility for enhancing oral bioavailability. Cilnidipine nanosuspension was formulated by Anti-solvent precipitation and Ultrasonication method using poloxamer 188, HPMC K4M and Poly vinyl alcohol as a stabilizer. • Melting point of drug was determined. It matches with standard value. • Physical compatibility study showed that the drug and excipients are physically compatible with each other. • Chemical compatibility study was performed using FTIR spectroscopy and its studies revealed that there was no change in major peaks, thus confirming no interaction between the drug and excipients. • Solubility of pure drug was determined. Cilnidipine was found to be insoluble in demineralized water. • Calibration curve of Cilnidipine was constructed in phosphate buffer pH 6.8 and it obeys Beer Lambert’s law. 8 formulations (F1 - F8) of Cilnidipine nanosuspension were prepared by Antisolvent precipitation and Ultrasonication using varying concentration of different polymers such as Poloxamer 188, HPMC K4M along with PVA (0.5% w/v) as the stabilizer. • The prepared formulations (F1 – F8) were evaluated for Drug content, Solubility determination, In vitro drug release study, ATR-FTIR spectroscopy, Particle size determination and poly dispersity index, Zeta potential determination and Morphology characterization by scanning electron microscopy. • All the formulations were evaluated for drug content which was in the range between 91.86% and 98.05%. • The solubility determination of all formulations in phosphate buffer pH 6.8 was found to be in the range of 0.0156 mg/ml to 0.0375 mg/ml. The results showed that the solubility of formulation was found to be higher in F1 (0.0375 mg/ml) and F5 (0.0358 mg/ml) compared with other formulations. The solubility of all formulations improved (from insoluble to slightly soluble) compared to pure drug of Cilnidipine. • The in vitro release was carried out for all formulations. The results showed that as the concentration of polymer was increased, the percentage drug release was decreased. Optimized formulations showed 98.69% and 96.49% drug release within 120 minutes, but pure drug released upto 22.46% only. • Based on higher solubility and increased in vitro drug release, F1 and F5 were selected as optimized formulations. The optimized formulations were characterized by ATR-FTIR spectroscopy, particle size determination and poly dispersity index and zeta potential determination. • The ATR-FTIR study demonstrated that there were no significant changes in the IR spectra of the pure drug and the liquid nanosuspensions F1 and for F5. • The particle size and poly dispersity index were determined using Horiba scientific nanoparticle analyzer. The particle size of formulation F1 was 189.6 nm and F5 was 381.4 nm (within nanometric range). • The polydispersity of formulations F1 and F5 were found to be 0.469 and 0.470 respectively, indicating uniformity of particle size within formulation. • The zeta potential study was determined by Horiba scientific zeta sizer. The zeta potential for the optimized formulations F1 and F5 were found to be -30.1 mV and -6.0 mV respectively which showed that the formulation is stable. • The shape and surface morphology of optimized formulations were observed by scanning electron microscopy. It shows that F1 and F5 formulation of nanosuspension has regular shape and homogenous size and has morphology that is different from that of the other formulations. • The release rate kinetic data for the best as a F5 formulation showed that the formulation provided good linearity was observed with the zero order (R2 = 0.974), the zero order kinetics explains the good release of the prepared nanosuspension over the period of 120 minutes. • The data were fitted into the Korsmeyer-Peppas equation which showed good linearity and the slope of the Korsmeyer-Peppas plot (n= 0.969) were found to be more than 0.45 indicating the diffusion mechanism is Case II transport. • The stability studies indicated that the optimized formulation F5 was stable and did not show any significant changes in the physical appearance and drug content at the end of 15 days and further carry out the stability studies on the formulations. The overall results indicate that in the formulation of Cilnidipine nanosuspension, the increased dissolution rate for the nanosuspension is primarily due to the reduction in the particle size. These findings indicate the suitability of formulation procedure for preparation of nanosized poorly water soluble drug with significantly improved in vitro dissolution rate and thus enhance fast onset of therapeutic drug effect. The results obtained in the study suggest that Cilnidipine nanosuspension may improve the patient compliance due to ease of administration. Hence, the developed formulation would be a possible alternative delivery system to conventional oral formulation to improve its bioavailability. FUTURE SCOPE: • In vivo study may be carried out. • Scale-up studies of the optimized formulations may be performed.
| Item Type: | Thesis (Masters) |
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| Additional Information: | 261911257 |
| Uncontrolled Keywords: | Formulation, Development, Evaluation, Cilnidipine Nanosuspension, treatment, Hypertension, Anti-Solvent Precipitation, Ultrasonication Method. |
| Subjects: | PHARMACY > Pharmaceutics |
| Depositing User: | Subramani R |
| Date Deposited: | 01 Nov 2022 17:06 |
| Last Modified: | 01 Nov 2022 17:06 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/20890 |
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