DEGRADATION KINETICS OF EFAVIRENZ AND SPARFLOXACIN IN AQUEOUS SOLUTION: INFLUENCE OF COSOLVENTS AND SURFACTANTS

ABSTRACT

Drug kinetics explains the rate of change of drugs with time. Most drugs are chemically unstable and the result obtained from the study of chemical kinetics of such drug is used to predict the length of time within which the pure drug or formulation will remain therapeutically potent and effective at a specified temperature.

Efavirenz and sparfloxacin are classified in class II of the Biopharmaceutical Classification System, which means they have poor water solubility and are highly permeable.

This study was aimed at determining the influence of cosolvents and surfactants on the rate constant K, of efavirenz and sparfloxacin.

The kinetic study of the drugs was done by introducing 1ml of the drug solution (20µg/ml) into various percentage solutions of the cosolvent or surfactant as applicable.  The solutions were transferred into vials, and placed into a water bath at a temperature of 60⁰C. At intervals of 30mins and up to 2hrs, samples were taken from the water bath and analyzed spectrophotometrically at a maximum wavelength of 304nm for sparfloxacin and 250nm for efavirenz. A plot of log percent drug concentration remaining of each drug versus time was carried out to obtain the rate constant K.

The log K of both drugs studied decreased considerably in the cosolvents and surfactants such as glycerol, propylene glycol, tween 80 and SLS employed in this study.

Altogether, the results suggests that glycerol, propylene glycol, polysorbate (tween) 80 and sodium lauryl sulphate (SLS) with 0.1M HCl and 0.1M NaOH  within the pharmaceutically acceptable non-toxic concentration can enhance the stability of sparfloxacin and efavirenz respectively when it is incorporated during formulation.

CHAPTER ONE

1.0 INTRODUCTION

Pharmaceutical product stability refers to the ability of such a product to retain its physical, microbiological, toxicological, chemical and preservative information specified on the container or closure system. (Kommanaboyina and Rhodes, 1999; Bajaj et al, 2012). It can also be defined as the time span within which a pharmaceutical product retains the same characteristics and properties it possessed at the time of packaging within specific limits throughout the period of its storage and usage. Stability test therefore assess how environmental factors affects the quality of a formulated product or drug substance, then the findings are used to predict the drug’s shelf life, determine appropriate storage requirements and recommend labelling instructions. Also for the regulatory approval of any formulation or drug, the results obtained during stability testing is a vital requirement. (Singh and Bakshi, 2000; Bajaj et al., 2012).

Conducting stability testing for pharmaceuticals involves complicated procedures which are expensive, time consuming and requires scientific expertise to ensure that quality, efficacy and safety is built into the drug formulation. The commercial and scientific success of a pharmaceutical product can be assured with the proper understanding of the process of drug development with the difficult and enormous procedures necessary to achieve a detailed development plan. Stability studies and pharmaceutical analysis are very crucial steps in the developmental stages of drugs as they are needed to determine and assure the quality, potency and purity of pharmaceutical ingredients as well as that of the products formulated. (Singh and Bakshi, 2000).

Stability testing can also be explained as a complicated process due to the fact that diverse number of factors influences the stability of pharmaceutical products. Stability of active ingredients, excipient and active ingredients interaction, the type of manufacturing process, type of dosage form, type of container or closure system used for packaging, light conditions such as heat and moisture encountered while shipping, handling and storage are some of the factors that influence stability. Also, degradation reactions such as reduction, oxidation, racemisation or hydrolysis which play significant roles in the stability of a pharmaceutical product also depend on other conditions such as pH, reactants concentration, catalyst, radiation etc., in addition to the nature of raw materials that was used and the period of time between the product manufacturing and final usage. Pharmaceutical products could also experience changes in clarity (for solutions), consistency, appearance, content uniformity, particle size and shape, moisture contents, pH and package integrity which can affect its stability. Those physical changes could be due to vibration, impact, abrasion and temperature changes such as freezing, thawing and shearing with chemical reactions like oxidation, solvolysis, racemisation, reduction etc which occur in pharmaceutical products that can lead to degradation product formation, loss of potency of active pharmaceutical ingredients (API), loss of excipient activity such as antimicrobial preservative action, antioxidants etc. (Carstensen et al., 2000). Microbiological changes such as microorganism’s growth in non sterile products and changes in the efficacy of the preservative can also affect pharmaceutical products stability. (Matthews, 1999; Bajaj et al., 2012).

It is very important to ensure that a pharmaceutical formulation remain stable throughout its shelf life in its packaging (Khalil, 2008; Naveed et al, 2016),  this is because changes in its physical, chemical, microbiological and therapeutic qualities in any constituent of the drug be it active or excipient will lead to its instability. (Yoshioka, 2000; Carstensen, 2000; Rockville, 2006; Naveed et al., 2016).