Assessment of Moisture Permeability and Closure Systems of High Density Polyethylene Plastic Bottles Used as Primary Packaging Containers for Moisture Sensitive Medicines

Introduction: Moisture permeability and a loose closure system might allow a significant gain of moisture into container and this could lead to significant loss of potency of drug sensitive to moisture and as well promoting the growth of microorganisms. Typical examples of the drugs sensitive to moisture include Tenofovir Disoproxil Fumarate (TDF). Product claimed to be a “Tight container” does not make it a tight container until proved practically. A plastic container is tight if “not more than one of the 10 tested containers exceeds 100 mg per day per L in moisture permeability. Objectives: The goal of this study was to determine rate of moisture permeability of selected High Density Polyethylene plastic bottles for packaging of moisture sensitive medicines in particular Lamivudine/Tenofovir Disoproxil fumarate tablets. Methodology: The determination of rate of moisture permeability was achieved by assessing closure systems of plastics as per USP 37 method, while the difference in absorption pattern was achieved by assessing the spectrum obtained through transmittance by Fourier Transform-Infrared (FT-IR). The plastic bottles were randomly selected from supplier A, B and C. Results: The plastic bottles from supplier A and B had an average moisture permeability of 12.57 and 51.55 mg/day/L with none of the containers exceeding moisture permeability of 100 mg/day/L whereas containers from supplier C had an average of 149.95 mg/day/L with seven of the containers exceeding of 100 mg/day/L. Conclusion: Containers from supplier A and B met the USP specifications hence could be used as primary packaging for moisture sensitive medicines whereas the containers from supplier C did not meet the USP specifications for them to be regarded as “Tight Containers” and hence, unsuitable for packaging of moisture sensitive medicines.

Pre-Formulation Development of Lamivudine 300 mg and Tenofovir Disoproxil Fumarate (TDF) 300 mg Fixed Dose Combination Tablets

Introduction: In this study, physical and chemical characteristics of Lamivudine, Tenofovir Disoproxil Fumarate (TDF) and potential excipients were systematically followed and documented [1]. Objective: The objective of this scientific work was to carry out pre-formulation studies including compatibility studies on Lamivudine and Tenofovir Disoproxil Fumarate with their potential excipients prior a direct compression process [2]. Methodology: The interaction was studied in three set of environments namely uncontrolled room conditions for Zone VI b (30°C ± 2°C), oven conditions in which the oven was set at 50°C and accelerated climatic conditions in which a climatic chamber was set at 40°C ± 2°C/75% ± 5% Relative Humidity (RH %). Sample preparation was done by mixing the amount of formulation excipients to active substances at a ratio of 1:10, whereas active substance to another active substance at a ratio of 1:1, active substance to coating materials at 1:4, coating materials to the whole set of excipients 1:4. The whole set of samples was geometrically mixed and triturated by mortar and pestle to very fine uniform powder to ensure homogeneity of the mixture. HPLC analytical method was used for simultaneous quantitative determination of lamivudine and tenofovir disoproxil fumarate. Transmittance of the mixture was determined by Near Infra-Red (NIR) technique. Results: The amount of Lamivudine as on day 0 was comparable to day 90 for in all tested conditions (Room, Oven and Climatic Chamber), whereas for Tenofovir Disoproxil Fumarate only the amount of the drug at Room (30°C ± 2°C) was comparable to results on day 90. A significant drop of amount of Tenofovir Disoproxil Fumarate (TDF) exposed to moisture (Climatic chamber at 40°C ± 2°C/75% ± 5% Relative Humidity (RH %)) and temperature of 50°C was observed. Colour change was observed for samples subjected to moisture (Climatic chamber at 40°C ± 2°C/75% ± 5% Relative Humidity (RH %)) and as well picked up in the NIR region 400 to 1500 cm-1 (Finger print region) by a significant shift in Transmittance. Conclusion: It can be concluded that microcrystalline cellulose, cross linked sodium carboxymethyl cellulose, magnesium stearate and sodium carbxymethyl cellulose can be compressed together with Lamivudine and Tenofovir Disoproxil Fumarate (TDF) to produce a pharmaceutically acceptable solid dosage form, tablet. The produced tablets should be packed in moisture and light protective containers as Tenofovir Disoproxil Fumarate (TDF) has diester linkages which can be hydrolysed into the active drug Tenofovir in the presence of moisture.