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Combinations of drugs are available in the market only to produce a single effect. To overcome this, a combination of three drugs namely α-arbutin, glutathione, and grape seed extract, are used to benefit the triple effect on the skin. The set forth study to formulate and evaluate medicated cosmetic cream in an effective curative strategy for derma to produce a triple effect. Medicated cosmetic cream containing triple bioactive agents formulated by the O/W dispersion method. Fourier transform infrared (FT-IR) and differential scanning calorimetry (DSC) was carried out for characterization. The formulated cream assessed for physical appearance, homogeneity, pH, viscosity, particle size analysis, spreadability, percentage yield, drug content, diffusion studies, release kinetics, acute dermal toxicity studies, and short-term stability studies. FT-IR and DSC studies revealed that no chemical interaction existed between the drug and excipients used. The optimized formula A5 revealed to be off white, semisolid, pleasant odor, smooth & slippery texture, non-greasy smear, easy to remove, and homogenous. The A5 cream exhibited a pH of 5.89, Viscosity of 1597.73 CPS, Spreadability of 20.86 g.cm/sec., the Particle size of 0.237%, Percentage yield of 98.8%, Drug content of 99.22 at 289 nm, 99.75 at 200 nm and 100.1 at 286 nm. The optimized cream demonstrated prolonged drug release 94.41% at 289 nm, 92.68 at 200 nm, and 92.78 at 286 nm up to 12 hrs. The optimized cream remained stable after the heating-cooling cycle at 4° C, 45° C and at room temperature. Furthermore, acute dermal toxicity studies showed the optimized formulation to be non-irritant, with no erythema, and no edema. The present study signified that the multiple combinations showed a better synergistic effect, superior efficacy, and multiple activities that resulted in the best, smooth, and stable medicated cosmetic cream.
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