In vitro-in vivo Pharmacokinetic correlation model for quality assurance of antiretroviral drugs

Introduction: The In vitro-in vivo pharmacokinetic correlation models (IVIVC) are a fundamental part of the drug discovery and development process. The ability to accurately predict the in vivo pharmacokinetic profile of a drug based on in vitro observations can have several applications during a successful development process. Objective: To develop a comprehensive model to predict the in vivo absorption of antiretroviral drugs based on permeability studies, in vitro and in vivo solubility and demonstrate its correlation with the pharmacokinetic profile in humans. Methods: Analytical tools to test the biopharmaceutical properties of stavudine, lamivudine y zidovudine were developed. The kinetics of dissolution, permeability in caco-2 cells and pharmacokinetics of absorption in rabbits and healthy volunteers were evaluated. Results: The cumulative areas under the curve (AUC) obtained in the permeability study with Caco-2 cells, the dissolution study and the pharmacokinetics in rabbits correlated with the cumulative AUC values in humans. These results demonstrated a direct relation between in vitro data and absorption, both in humans and in the in vivo model. Conclusions: The analytical methods and procedures applied to the development of an IVIVC model showed a strong correlation among themselves. These IVIVC models are proposed as alternative and cost/effective methods to evaluate the biopharmaceutical properties that determine the bioavailability of a drug and their application includes the development process, quality assurance, bioequivalence studies and pharmacosurveillance.

Physicochemical properties of water quality of Imeh, Edegelem and Chokocho communities located along Otamiri-oche River in Etche Ethnic Nationality of Rivers State, Nigeria

Some physiochemical properties of water quality of Otamiri-oche River which runs through Imeh, Edegelem and Chokocho Communities in Etche ethnic nationality of Rivers State, Nigeria were investigated. Samples were collected in triplicate from the three different locations along the river in both rainy and dry seasons. Each sampling points is located 500m away from the successive one, and the samples were taken from the open river at the zone extending beyond the shoreline. Samples were stored in ice packs and immediately taken to the laboratory to investigate some selected physico-chemical characteristics. Also, bacteriological study was carried out on the samples. The laboratory results of the selected physico-chemical parameters when compared with the world health organization (WHO) standard showed that all the selected physico-chemical parameters were within the world health organization (WHO) permissible in both rainy and dry season except pH. For rainy season, the pH values were 5.00±0.00, 5.40 ±0.40, and 5.40± 0.30 for Imeh, Edegelem and Chokocho respectively. For the dry season, the pH values were 5.83± 0.01, 5.56±0.01, 5.90±0.01 for Imeh, Edegelem and Chokocho respectively. Also magnesium hardness exceeded the World Health Organization (WHO) permissible limit in rainy season only. The results of bacteriological study showed that all the sampling locations contained high numbers of coliform bacteria in both rainy and dry seasons. The number of coliform bacteria during rainy season was 25.00±0.00, 25.00±0.00, and 35.00±0.00 for Imeh, Edegelem and Chokocho respectively. Those of dry season were 93.00±3.55, 56.66±4.49, and 35.60±4.17 for Imeh, Edegelem and Chokocho respectively. The difference between the rainy and dry season was tested statistically using the t-test. The results of the statistical analyses showed a significant difference (p<0.05) between the rainy and dry seasons.

In-vitro evaluation of the quality of Paracetamol and Co-trimoxazole tablets used in Malawi based on pharmacopoeial standards

Objectives This study was an in-vitro evaluation of different brands of paracetamol and cotrimoxazole tablets, used or found in Malawi, based on Pharmacopoeia standards, in order to ascertain the existence and extent of substandard medicines in Malawi and to give an overview of their distribution in the public and private sectors. Methodology A cross-sectional analytical study was conducted using 11 samples each of paracetamol and cotrimoxazole tablets. Stratified random sampling was used to collect samples. Samples were analyzed using HPLC and Spectrophometric methods as outlined in the BP-2007 and USP-32 at the National Drug Quality Control Laboratory (NDQCL)-Lilongwe (under Pharmacy Medicines and Poisons Board-PMPB) and Orient Pharma Co. Ltd of Taiwan. The results were analyzed using Epi Info. Results and discussion Fifty percent of samples (n=22) were not registered in the country by the PMPB as required by the PMP Act with the majority of those coming from public health facilities. All paracetamol and cotrimoxazole samples complied with identification tests using spectrophotometric and HPLC method. Overall, 27.3% of samples failed to meet the BP-2007 standards for Active Ingredient content, while 22.7% of the samples failed the Friability test. The results from Malawi are similar in magnitude to those within surrounding countries in Africa. Conclusion This pilot study provides objective evidence to show that substandard and unregistered paracetamol and cotrimoxazole are present and being used in Malawi, and thus posing a considerable hazard to public health in Malawi. PMPB, together with the Ministry of Health, must continue to develop a quality assurance system to ensure that medicines are randomly and routinely checked.