Analytical Study on Some Drugs Used for Treatment of Acne and Melasma

Abstract

Part I: General Introduction. It includes a general introduction on melasma disease and acne vulgaris including prevalence, etiology, effect on quality of life and treatment options.

Part II: Literature Review. It includes a detailed review on the studied drugs, Tretinoin, Eusolex, Hydroquinone, Hydrocortisone acetate and Fluocinolone acetonide. This review explains chemical and physical drug properties, pharmacology, structure activity relationship, pharmacokinetics and different analytical methods reported in literature.

Part III: Spectrophotometric Analysis. This part consists of four sections: Section A: Mathematical filtration of quaternary mixture to the zero order spectra of its individual components. In this section, Simple, accurate and precise validated UV spectrophotometric methods have been described here for the simultaneous determination of Tretinoin (TN), Eusolex (EX), Hydroquinone (HQ), and Hydrocortisone acetate (HC) in their dosage form. Simultaneous determination of these four drugs was a major challenge till now. Each spectrum was filtered alone to its zero-order absorption spectrum (D0) form getting spectra typical to each pure component separately. Four methods were applied depending upon constants obtained from extended regions of partially overlapped spectra in the zero or first derivative forms. The methods applied are constant multiplication coupled with spectrum subtraction method (CM-SS), derivative transformation coupled with spectrum subtraction method (DT-SS), constant value method (CV), and concentration value (conc.value) method. The partially overlapped spectra of TN and EX in the mixture were obtained by CM-SS in their zero-order form allowing direct measurement at their λmax, while the resolved binary mixture of HQ and HC obtained by spectrum subtraction; was determined by derivatization, and transformed to their zero order by DT-SS. The methods applied to the quaternary mixture under study were successfully applied for the simultaneous determination of the four drugs in synthetic mixtures and in their combined dosage form Tritospot® cream. Section B: Three Different Approaches Based on Derivative Ratio Spectra for Spectrophotometric Resolution of Quaternary Mixture in Semisolid Dosage Form. Several spectrophotometric techniques were introduced for the determination of a mixtures of Tretinoin (TN), Hydroquinone (HQ), and Fluocinolone actonide (FA), in presence of the preservative; Methyl Paraben (MP), without any separation procedure, taking into consideration the presence of two minor components and the severe overlap of their spectra. Constant multiplication coupled spectrum subtraction resolved the quaternary mixture into the zero-order absorption spectrum of TN alone and a severely overlapped ternary mixture of HQ, FA, and MP. Three approaches based on the derivative ratio spectra were applied to resolve this ternary severely overlapped mixture which are: derivative ration zero crossing point method, factorized derivative ratio method, and double divisor derivative ratio method. The proposed methods were successfully applied for the simultaneous determination of the three drugs in presence of MP in synthetic mixtures and in their combined dosage form Trimelasma® cream with very good accuracy and precision. Section C: Comparative study between PLS and PCR in determination of Quaternary Mixtures in Tritospot® Semisolid Dosage Form. Two methods of analysis were conducted that need computational procedures by the MATLAB® software. The two multivariate methods named partial least square (PLS) and principal component regression (PCR) depend on a large number of variables that lead to extraction of the maximum amount of information required to determine the component of interest in the presence of the other. Good accurate and precise results were obtained from the two methods for determining Tretinoin (TN), Eusolex (EX), Hydroquinone (HQ), and Hydrocortisone acetate (HC) in synthetic mixtures and pharmaceutical formulation. The methods were simple and non-time consuming and achieved successful and precise application on dosage form Tritospot® cream.