Analytical Method Development, Validation and Degradation Studies of Dosage Forms of Montelukast and Desloratadine

Abstract

The present thesis work entitled “Analytical Method Development, Validation and Degradation Studies of Dosage Forms of Montelukast and Desloratadine” is divided into 10 chapters as described below in brief. Chapter 1 describes the general introduction about causes, symptoms and treatment of allergy. Among the anti-allergic agents, the selected drugs montelukast (leukotriene receptor antagonist) and desloratadine (second generation tricyclic antihistamine) has been discussed in detail with their drug profile which is very important in method development. Chapter 2 give the detailed review of literature for analytical methods reported in public domain for determination of montelukast and desloratadine in bulk, formulations and different biological matrix. Chapter 3 is about the aim and objectives of the present work. The aim of this research is to develop and validate new analytical methods for simultaneous determination of montelukast and desloratadine in their combined dosage form and extending the application of developed method for degradation study of montelukast and desloratadine Chapter 4 describes the UV-Visible spectrophotometric method for simultaneous estimation of montelukast and desloratadine in tablet dosage form. The method was developed using methanol as a solvent for both the drugs owing to their high degree of solubility in methanol. The absorbance maxima for montelukast and desloratadine was found to be 344 and 238 nm respectively. Estimation of drugs from formulation was carried out by deriving simultaneous equation method. Beer’s law was obeyed between 2-24 and 2-20 μg/mL for montelukast and desloratadine respectively. Limit of detection values for montelukast and desloratadine were 0.310 and 0.190 μg/mL respectively, while limit of quantification values were 0.940 and 0.590 μg/mL for the selected drugs respectively. The method was applied for assay of drugs from marketed tablet formulation. Chapter 5 describes the high performance liquid chromatographic method for simultaneous estimation of the drugs from formulation. The method was developed using C18 column (150 X 4.6 mm, 5 μ). The drugs were eluted using mobile phase A (ammonium acetate buffer pH 5.5) and mobile phase B (methanol) in gradient mode. Column eluent was monitored at 240 nm using variable wavelength detector. The developed method was checked for various chromatographic parameters like, theoretical plates, asymmetry and resolution of the analytes.The method was validated as per ICH guideline for parameters like linearity, limit of detection and quantification, precision and robustness. The method was extended for its’ application for simultaneous determination of both the drugs from tablet formulation and content uniformity. Chapter 6 is about the stability indicating assay method for simultaneous estimation of montelukast and desloratadine and kinetic study of degradation of montelukast in acidic and oxidative degradation conditions. Montelukast and desloratadine were exposed to acidic, alkaline, oxidative, photo and thermal degradation stress conditions. The degraded samples were then analyzed using the developed HPLC method. In acidic degradation conditions (0.1 M methanolic HCl, 30 min) montelukast showed extensive degradation with one prominent degradation product, while desloratadine does not show any degradation. Both the drugs were found to be relatively stable in alkaline degradation conditions (0.1 M methanolic NaOH, 30 min). In peroxide degradation condition (3 % w/v H2O2, 30 min) montelukast showed around 22% degradation with formation of one prominent degradation product. In photolytic degradation condition (40 days, sunlight) montelukast showed around 25% degradation with generation of four degradation products. Upon exposure to thermal stress condition (80 0C, 30 days) montelukast showed around 7 % degradation. Desloratadine was found to be unaffected in all stress conditions. Based on the observation that montelukast is highly susceptible to acid and peroxide degradation conditions; the kinetic study for these degradation was carried out. The montelukast followed second order of reaction in acidic degradation conditions, while it showed first order of reaction in peroxide degradation kinetic study. Chapter 7 describe the development and validation of high performance thin layer chromatographic method for simultaneous estimation of both the drugs from tablet formulation. The method was developed using pre-coated silica gel 60 F254 on aluminum plate (10 × 10 cm, 0.2 mm layer thickness) procured from E Merck Ltd (India). The samples were applied using Camag 100 μL applicator syringe (Hamilton, Bonaduz, Schweiz) and Camag Linomat Vapplicator with N2 pressure. Camag twin trough chamber (20 x 10 cm and 10 × 10) with stainless steel lid were used for development of the plates. The developed plates were observed through UV cabinet with dual wavelength (254 and 366 nm) and scanned using Camag TLC scanner 3. The mobile phase used was n-butanol: methanol: ethyl acetate: ammonia in the ratio of 3.0: 2.5: 5.0: 0.5. The method was validated according to ICH guideline and applied for assay and content uniformity of both the drugs from tablet formulation. The developed method was extended for stability indicating assay of both the drugs. The HPTLC method was able to resolve acid and peroxide degradation products from montelukast peak.