Formulation and evaluation of phenylephrine and Ketrolac loaded ophthalmic self-nanoemulsifying drug delivery system

Abstract

Aim: The current work aims to develop and evaluate Phenylepherine and Ketorolac loaded Self Nanoemulsifying Drug Delivery System to improve their solubility.

Preparation design:  Castor oil was used as the oil, Span 80 as the surfactant, and poloxamer as the co-surfactant in a series of SNEDDS using Phase titration method.

Methodology: As part of the preformulation studies, a solubility test was performed on Phenylephrine and Ketrolac, and calibration curves were developed. To construct pseudo ternary phase diagrams, oil (CAPTEX-200) was mixed with various surfactant and cosurfactant ratios (TWEEN80/PEG-200) in varied concentrations. Span-80 and Poloxomer 188 were used to obtain the desired optimization of co-surfactants. SNEDDS were carried out using the Phase titration technique using castor oil as the carrier oil, Span 80 as the surfactant, and poloxamer as the co-surfactant in a series of SNEDDS. Through the use of SEM, thermal stability tests, and in vitro drug release of phenylephrine and ketorolac, the produced SNEDDS were assessed for phase separation, percent transmittance, drug loading, surface shape and size, and drug release.

Results: Phenylepherine and Ketrolac have been discovered to have maximum wavelengths (max) of 236nm and 241nm, respectively. Calibration curves for phenylepherine and ketorolac were drawn using pH 7.4 phosphate buffer and 1.2 pH 0.1N hydrochloric acid, respectively, as the pH 7.4 phosphate buffer and 1.2 pH 0.1N hydrochloric acid, respectively. They demonstrate high correlation and linearity in the concentration range of 5 to 30 g/ml, with R2 values of 0.998 and 0.997, respectively, within the concentration range. A total of nine formulations with Phenylepherine were tested for thermodynamic stability and were selected for further characterization. The formulations P4, P5, P6, P7, P8, and P9 with Phenylepherine and three formulations with ketrolac (K4, K5, and K6) were tested for thermodynamic stability and were selected for further characterization. P4 and P5 were found to be less clear and turbid based on percent transmittance. The formulations P6, P7, P8, and P9 are clear and transparent, whereas P10 is opaque. K2, K3, K4, K5, K6, and K8 were less translucent and clear than the other colours. In the SEM, it was discovered that the majority of the SNEDDS particles had a reasonably spherical shape, that the surface of the particle exhibited a typical smoothness, and that the particle size was in the micrometre range. It was established that the maximal drug release from the formulations Phenylepherine SNEDDS (P9) and Ketorolac SNEDDS (K9) occurred at 30 minutes (102.20 2.76 percent and 100.74 2.80 percent, respectively) based on in vitro drug release studies.

Conclusion: All of the aforementioned studies, taken together, revealed a significant increase in the bioavailability and solubility of Phenylepherine and ketorolac when administered in the form of SNEDDS. Finally, it can be stated that SNEDDS is a potentially useful approach for increasing the solubility, dissolving rate, and bioavailability of drugs and other pharmaceutical products.