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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.

The comparison of two methods based on online solid phase extraction-liquid chromatography with UV (SPE-LC-UV) or mass spectrometry detection (SPE-LC-MS/MS) for the simultaneous quantification of sulfamethoxazole (SMZ) and trimethoprim (TMP) is presented. The methods were validated and proved to be accurate. The analysis of standard samples for SMZ at concentrations of 0.5, 1.5, 25 and 50microg/mL demonstrated a relative standard deviation of less than 6% for both methods (n=18), while TMP samples at concentrations of 0.05, 0.15, 1.5 and 5.0microg/mL were analyzed with R.S.D. of less than 4% (n=18). The method with mass spectrometric detection was approximately six times more sensitive than the method with ultraviolet detection. The total run time for the SPE-LC-MS/MS was 2.5min per sample as opposed to 18.0min for the SPE-LC-UV method. The method with MS detection in comparison with UV detection proved to be more rugged and was successfully applied to pharmacokinetics studies.

The effect of hydroxypropyl-beta-cyclodextrin (HPbetaCD) on the chemical stability of sulfamethoxazole and trimethoprim (co-trimoxazole) under oxidation stress at 50 +/- 2 degrees C was investigated. The concentrations of sulfamethoxazole and trimethoprim in aqueous solutions (pH 5.4) containing 0, 1%, 2%, 5%, 10% and 15% w/v hydroxypropyl-beta-cyclodextrin were measured by HPLC. Both sulfamethoxazole and trimethoprim degradation appeared to follow pseudo-first order kinetics in the presence and in the absence of hydroxypropyl-beta-cyclodextrin. The observed half-lives for sulfamethoxazole and trimethoprim in 15% w/v hydroxypropyl-beta-cyclodextrin were 910 h and 609 h respectively, 11.8 and 3.4 times greater than in solutions without hydroxypropyl-beta-cyclodextrin. Using a Lineweaver-Burk equation, the half-lives for sulfamethoxazole and trimethoprim outside the complex in a solution containing 15% w/v hydroxypropyl-beta-cyclodextrin were estimated at 77 h and 193 h respectively, whereas inside the complex the half-lives were estimated at 850 h and 821 h. In terms of relative increases in stability under oxidation stress the half-lives for sulfamethoxazole and trimethoprim inside the complex were 11.0 times and 4.2 times greater than their half-lives outside the complex. In conclusion, chemical stability of sulfamethoxazole and trimethoprim in co-trimoxazole aqueous solutions under oxidation stress at 50 +/- 2 degrees C can be increased using hydroxypropyl-beta-cyclodextrin as a molecular inclusion excipient.

Background: Although the experimental assessment of co-trimoxazole by use of derivative spectrophotmetry underscores the usefulness of this method due to its relative simplicity with which it can be carried out over the official United States Pharmacopoeia (USP) high pressure liquid chromatography (hplc) methods for this drug, suitable optimum conditions ought to be refined for its universal acceptability., Objective: The objective of the present work was to obtain the optimum pH level for the UV assessment of co-trimoxazole., Methods: The aqueous solutions of the individual drugs and their binary mixtures were buffered with Sodium Acetate-Acetic Acid buffer in the pH ranges 2-7 and scanned on zero order and on first-order derivative at the wave length between 200- 300 nm., Results: At the same drug solution concentrations, spectral shifts occurred with change in pH, especially between the wavelengths 200 and 240 nm, only seeming to converge from approximate wavelength 260 nm onwards. Absorbance fluctuations were also observed at the same drug concentrations in the pH range 2 to 3.5 and 5 to 7 when the solutions were scanned, even at the wavelength where the spectra seem to converge. However there were no absorbance differences between pH 4 and 5., Conclusion: The UV spectrophotometric method is dependent on the optimum pH and this has been found to range from 4 to 5.

A simple and rapid indirect potentiometric titration of sulphamethoxazole in the presence of trimethoprim contained in co-trimazole tablets is described. The method is based on the formation of a complex of sulphamethoxazole with a known excess of silver ions and the titration of unreacted silver ion potentiometrically using an inexpensive lab-made copper based mercury film electrode (CBMFE). The titration conditions have been optimized for the determination of 1.0-10.0 mg of sulphamethoxazole in pure and dosage forms. The precision and accuracy of the method have been assessed by the application of lack of fit test and other statistical methods. Overall mean recovery and relative standard deviations obtained were 99.88% and 1.32% (n=7) respectively. No interference was caused by other excipients present in pharmaceutical dosage forms. The application of this method for sulphamethoxazole assay in the presence of trimethoprim in tablets was validated by the comparison of results obtained by the proposed method with that of the British Pharmacopoeia (BP) method using F- and t-statistical tests of significance.

Release profiles and dissolution kinetics of active substance, viz. sulfamethoxazol (SMO), trimethoprim (TMP), and oxytetracycline hydrochloride (OTC) from capsulated multicomponent dispersions was studied in a flow-cell apparatus at 37 degrees C by using a dissolution medium of 0.1 mol/l HCl. The results revealed that the relative dissolution efficiency (DE) and dissolution profiles of one active ingredient were affected by the presence of the two others. Vitamin C added caused the decreased the dissolution rate constants (K) and DE--values of all the active substances studied.