An Approach to Drug Stability Studies and Shelf-life Determination

Abstract

The main objective of carrying out stability studies of the drug product is to establish shelf life of drug during storage. Stability of drug is defined as “The capability of a particular formulation in a specific container/closed system, to remain within its physical, chemical, microbiological, therapeutic, and toxicological specifications throughout its shelf life”. As mentioned in the International Conference on Harmonization (ICH) guideline Q1A (R2), stability studies are commonly the activity on the critical path to regulatory filing and approval. Stability studies are of different types and different methods are useful for the determination of stability like real-time stability testing, accelerated stability testing, retained sample stability testing and cyclic temperature stress testing. pH and temperature are the main factors influencing the stability of the drug. The pH-rate profile (log(k)vs pH) is the pH dependence of the specific rate constant of degradation of compounds. Forced degradation includes deterioration of new drug substances and products at more severe conditions than the accelerated conditions and it indicates the accuracy of stability-indicating methods. The different conditions applied during the forced degradation include hydrolytic, oxidation, photolytic and thermal stress etc. The techniques utilized for evaluation of stability studies can be LC-MS/MS, HPLC-DAD, HPLC-MS, HPLC-UV, HPTLC, TLC, LC-NMR etc. amongst them some techniques shows high sensitivity and resolution power to establish more effective stability-indicating method while for shelf life estimation of drugs and products the different methods mentioned are FDA’s method, the direct method, inverse method, simulation results and Garret and Carper method. Thus stability testing of pharmaceutical products inputs specific scheme in the evolution of a new drug as well as new formulation.

Guidelines on Stability Studies of Pharmaceutical Products and Shelf Life Estimation

“…Nevertheless, system performance and control for drift and discontinuity ensuing from alters in both reagents and instrumentation ought to be scrutinized. [8,9] 3.2 Accelerated stability testing This nervy testing stability method is utilized for the reasoning of product stability through the storage of product at various inebriated (warmer than ambient) temperatures and to determine the quantity of heat required to cause accelerated degradation of the product. This message enables to foretell stability of medicine product, its shelf life and to see storage condition by providing a substance of examination deciding formulations and thus diminution the development schedule.…”

“…A commonsensible statistical discourse in accelerated stability projections based on the Arrhenius equation unremarkably requires that at least four stress temperatures be used. Many accelerated stability testing models are based on the Arrhenius equation (1) and modified Arrhenius equation (2) [8][9][10] = + ∆ ………………….. (1) Where k= degradation rate/s, A = frequency factor/s, ΔE = activation energy (kJ/mol), R = universal gas constant (0.00831 kJ/mol), T=absolute temperature (Kelvin). Where k1 and k2 are rate constants at temperatures T1 and T2 expressed in degree Kelvin; Ea is the activation energy; R is the gas constant.…”

Stability of Paracetamol Instant Jelly for Reconstitution: Impact of Packaging, Temperature and Humidity

“…The major aim of the pharmaceutical stability testing is to supply sensible confirmation that the products will stay at a satisfactory quality level when reaching the marketplace and until the patient uses the last unit of the product [ 4 ]. In general, the stability study is divided into an accelerated stability test (40 ± 2 °C/75 ± 5% RH) for 6 months, intermediate study (30 ± 2 °C/65 ± 5% RH) for 6 months, and long-term study (25 ± 2 °C/60 ± 5% RH or 30 ± 2 °C/65 ± 5% RH) for 12 months or longer [ 5 ]. The exact storage conditions, time points for testing, and study duration differ based on the climate zones as defined by the ICH guidelines and might be subject to local authority regulations.…”

A Novel Stability Study of Simvastatin Generic Tablet in Public Pharmacy Facilities of Purwakarta District, Indonesia

“…Drug stability can be defined as the durability and efficacy of a product within the prescribed limit of storage and use period, to maintain the same traits and characteristics possessed at the time of packaging (Allen, 2013;Melo et al, 2014;Tembhare et al, 2019). Environmental factors such as temperature, light, radiation, air (especially oxygen and carbon dioxide), and humidity may have a detrimental effect on the stability of a particular product (World Health & Preparations, 2018a).…”

“…Environmental factors such as temperature, light, radiation, air (especially oxygen and carbon dioxide), and humidity may have a detrimental effect on the stability of a particular product (World Health & Preparations, 2018a). If the storage can be controlled to be within the conditions as recommended by the manufacturer, the proposed shelf life would ascertain the stability of the active ingredient and subsequently the effectiveness of the drugs (Bajaj et al, 2012;Tembhare et al, 2019).…”