The development and assessment of sustained release nevirapine tablets

The use of antiretroviral (ARV) agents in the management of HIV/AIDS has significantly improved the lifestyle and wellbeing of patients. Despite the success that has been achieved with the use of ARV therapy, the occurrence of adverse effects and unpredictable bioavailability associated with most of these drugs remains a major concern. Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that is used in combination with other ARV compounds for the treatment of HIV-1 infections. It is also used for the prevention of mother to child transmission of the HIV-1 virus. NVP is a Biopharmaceutics Classification System (BCS) Class II compound. Although NVP exhibits good oral absorption, it induces self-metabolism leading to low and sometimes unpredictable bioavailability. NVP is commercially available as an immediate release and extended release dosage form, viz., Viramune® XR. Formulation of a generic sustained release (SR) dosage form for once daily dosing would result in delivery of constant amount of the drug to the circulation, reduce dose related adverse effects, improve patient compliance to medication and reduce the costs of therapy. A simple RP-HPLC method was developed and optimised using a central composite design approach. The method was validated using ICH guidelines and was found to be linear, precise, specific and accurate for the analysis of NVP both in bulk and dosage forms. Direct compression was used as the method of tablet manufacture. Different polymers were assessed for suitability as rate retarding polymers and included Methocel® K4M, Carbopol® 71G NF and Eudragit® RSPO. Powder blends were assessed for flow properties using the angle of repose, bulk and tapped density, Carr’s Compressibility index and Hausner’s ratio. The traditional approach of changing the amount of polymers and diluents systematically to achieve a desired NVP release profile was used for the development of a preliminary formulation. Response surface methodology was used for the optimisation of the formulation using a Box-Behnken quadratic design. Physical characteristics of the tablets such as thickness, weight, hardness, tensile strength and friability were assessed and the tablets passed Pharmacopoeial testing. NVP assay and content uniformity were assessed using a validated RP-HPLC method. Initially, USP Apparatus 2 was used to study NVP release over a 24 hour period and subsequently dissolution studies were performed using USP Apparatus 3 as it can be used to simulate GIT conditions. The dissolution profiles generated were used to determine the agitation rate for USP Apparatus 3 that would be equivalent to an agitation rate of 50 rpm when using USP Apparatus 2. The effect of the mesh screen pore size, buffer molarity strength and concentration of surfactant on NVP release were also investigated in order to select discriminatory dissolution test conditions for the test formulation. Dissolution profiles were compared to those of the commercially available Viramune® XR using the FDA recommended difference (f1) and similarity (f2) factors. The calculated values for f1 and f2 revealed that the dissolution profile for the optimised formulation that was identified was statistically similar to Viramune® XR. In vitro release data were fitted to different kinetic models to study the release kinetics of NVP. The overall mechanism of NVP release was best described using the Korsmeyer-Peppas diffusion exponent value, n. NVP release was found to be anomalous, implying that the release was influenced by a combination of diffusion, swelling and polymer chain relaxation. The Hixson-Crowell model revealed that there was constant change in surface area of the dosage form suggesting that erosion and swelling were significant factors affecting NVP release from the hydrophilic matrix technology. The release kinetics data were also used to design the optimised formulation. Tablets manufactured using the optimised formulation were subjected to water uptake and erosion studies and the results revealed that swelling and erosion occur simultaneously. The effects of pH and molarity on the swelling and erosion of the tablets were also investigated. The data suggest that increase in pH resulted in a slight increase in swelling while an increase in molarity did not have a significant effect on swelling. The change in pH did not have a significant effect on erosion while an increase in molarity strength resulted in a decrease in matrix erosion. The effect of HPMC grade on swelling, erosion and NVP release revealed that the grade of HPMC used had a significant effect on NVP release, with the release rate decreasing, swelling increasing and erosion decreasing as the viscosity of the HPMC grade increased. The effect of the particle size of MCC on NVP release was also studied by manufacturing tablets containing different grades of MCC and these studies revealed that particle size did not appear to have a significant effect on NVP release. Similarly the use of different types of lactose did not appear to have a significant impact on NVP release. In conclusion a sustained release NVP tablet formulation that has the potential for further development and optimisation has been developed, assessed and manufactured successfully and has been shown to exhibit similar dissolution behaviour to Viramune® XR, a commercially available NVP extended release product

The development, manufacture and evaluation of sustained release gastric-resistant isoniazid and gastroretentive microporous rifampicin microspheres

Expected release date-April 202

Improved Stability of Rifampicin in the Presence of Gastric-Resistant Isoniazid Microspheres in Acidic Media

The degradation of rifampicin (RIF) in an acidic medium to form 3-formyl rifamycin SV, a poorly absorbed compound, is accelerated in the presence of isoniazid, contributing to the poor bioavailability of rifampicin. This manuscript presents a novel approach in which isoniazid is formulated into gastric-resistant sustained-release microspheres and RIF into microporous floating sustained-release microspheres to reduce the potential for interaction between RIF and isoniazid (INH) in an acidic environment. Hydroxypropyl methylcellulose acetate succinate and Eudragit® L100 polymers were used for the manufacture of isoniazid-loaded gastric-resistant sustained-release microspheres using an o/o solvent emulsification evaporation approach. Microporous floating sustained-release microspheres for the delivery of rifampicin in the stomach were manufactured using emulsification and a diffusion/evaporation process. The design of experiments was used to evaluate the impact of input variables on predefined responses or quality attributes of the microspheres. The percent degradation of rifampicin following 12 h dissolution testing in 0.1 M HCl pH 1.2 in the presence of isoniazid gastric-resistant sustained-release microspheres was only 4.44%. These results indicate that the degradation of rifampicin in the presence of isoniazid in acidic media can be reduced by encapsulation of both active pharmaceutical ingredients to ensure release in different segments of the gastrointestinal tract, potentially improving the bioavailability of rifampicin

Development and assessment of a USP Apparatus 3 dissolution test method for sustained-release Nevirapine matrix tablets

Dissolution testing is a quality control tool used to assess batch-to-batch performance of dosage forms, thereby providing continued assurance of product quality. Analytical methods for the assessment of pharmaceutical product quality must be validated according to regulatory guidelines to ensure that tests are reliable and valid. Agitation rate, mesh pore size, surfactant concentration, and dissolution medium molarity are experimental parameters that may affect nevirapine (NVP) release and were investigated and optimized to ensure that consistent, reliable, and valid results using Apparatus 3 were produced. Agitation rate was investigated to establish an equivalent response to that observed for NVP release using Apparatus 2 at 50 rpm. A reciprocation rate of 5–10 dpm produced dissolution profiles that were similar to those observed using Apparatus 2. An increase in the molarity of the dissolution medium slightly increased the release rate of NVP, and a 50 mM buffer maintained at pH values mimicking gastrointestinal tract (GIT) conditions was selected for all experiments. With the addition of 2% sodium lauryl sulfate (SLS) to the dissolution medium, >80% NVP was released from the tablets over the test period. The NVP release rate increased with an increase in the mesh pore size; however, the extent of release was not affected by this parameter. Dissolution test samples were analyzed using HPLC, and dissolution methods were validated for NVP stability in the dissolution medium, specificity, linearity and range, repeatability, intermediate precision, and accuracy as defined by ICH. The dissolution method used for testing NVP tablets can be regarded as an appropriate tool for the evaluation of sustained-release (SR) NVP formulations and the impact of formulation composition and product quality attributes on drug release

A Comparison of the Arbitrary Set Fifty Percent Pass Mark Standard and Grade Point Average Attainment for Pharmacy Students at the University of Zambia: Implications for High-stakes decisions in Assessments

In many higher learning institutions and Health Professions Education (HPE) programmes in particular, there exists varying standard setting methods for assessment, certification and graduation of students’ academic performance. In Zambia, the historic arbitrary set 50% pass-fail standard is predominant in most health professions’ training programmes. Scientific validation of this practice, however, remains scarce. The aim of this study was to compare the academic performance on the historic arbitrary set 50% pass-fail standard to the Grade Point Average (GPA) score attainment for pharmacy students examined between 2013 and 2017 at the University of Zambia. A cross-sectional study was conducted with a total of 445 randomly selected final examination results for undergraduate pharmacy students examined between 2013 and 2017 at the University of Zambia. The data was analysed using Stata 13 and GraphPad Prism 5.  For all the statistical tests conducted, normality of the data was checked using the Shapiro-Wilk test. There was statistically significant difference between the historic arbitrary set 50% pass-fail standard and the course-specific examination composite score attainment in all the courses (P<0.0001). Additionally, there was a statistically significant difference between the examinees’ GPA score attained and the acceptable GPA score of 3.0 (Median GPA 1.75; IQR: 0.75-2.25 and 1.67; IQR: 1.0-2.0) for the fourth and fifth-year examinees respectively). The comparison of the academic performance on the arbitrary 50% pass-fail standard and GPA score attainment for pharmacy students revealed that despite students demonstrating ability to attain high course-specific composite scores using the arbitrary set 50% pass-fail standard, the attained median GPA score was statistically significantly less than the minimum acceptable GPA score of 3.0. While the 50% pass-fail standards’ precision to detect academic performance maybe questioned, the findings suggests that the incorporation of a credit point and GPA system for making assessment decisions to rate students, certification and graduation requirements in Health Professions Education may offer better precision and prediction to detect academic performance and competency attainment

Antibiotic use and stewardship indicators in the first- and 2 second-level hospitals in Zambia : findings and implications 3 for the future

There are increasing concerns with growing rates of antimicrobial resistance (AMR) across Africa including Zambia, enhanced by inappropriate utilization of antibiotics across the sectors. There is a need in hospitals to document current prescribing patterns via point prevalence surveys (PPS) alongside recognized indicators to improve future use. The findings can subsequently be used to develop and instigate appropriate antimicrobial stewardship programs (ASPs) to improve the quality of future antimicrobial prescribing across Zambia. This includes encouraging the pre-scribing of 'Access' over 'Watch' and 'Reserve’ antibiotics where pertinent. Methods: A PPS was undertaken using the WHO methodology among ten first- and second-level public hospitals across the ten provinces of Zambia. A sampling process was used to select the hospitals. Results: The prevalence of antibiotic use among the in-patients was 307/520 (59.0%), with a high rate of empiric prescribing of ceftriaxone at 36.1% of all antibiotics prescribed (193/534). The reason for antibiotic use was recorded in only 15.7% of occasions and directed treatment prescribed in only 3.0% of occasions. Compliance with national Standard Treatment Guidelines (STGs) was also low at only 27.0% of occasions. Conclusion: High empiric prescribing, limited documentation of the rationale behind antibiotic prescribing, high use of ‘Watch’ antibiotics, and limited compliance to STGs among surveyed hospitals require the urgent instigation of ASPs across Zambia to improve future prescribing

Biocompatibility of Biomaterials for Nanoencapsulation: Current Approaches.

Nanoencapsulation is an approach to circumvent shortcomings such as reduced bioavailability, undesirable side effects, frequent dosing and unpleasant organoleptic properties of conventional drug delivery systems. The process of nanoencapsulation involves the use of biomaterials such as surfactants and/or polymers, often in combination with charge inducers and/or ligands for targeting. The biomaterials selected for nanoencapsulation processes must be as biocompatible as possible. The type(s) of biomaterials used for different nanoencapsulation approaches are highlighted and their use and applicability with regard to haemo- and, histocompatibility, cytotoxicity, genotoxicity and carcinogenesis are discussed

Nano-biomimetic drug delivery vehicles: potential approaches for COVID-19 treatment

The current COVID-19 pandemic has tested the resolve of the global community with more than 35 million infections worldwide and numbers increasing with no cure or vaccine available to date. Nanomedicines have an advantage of providing enhanced permeability and retention and have been extensively studied as targeted drug delivery strategies for the treatment of different disease. The role of monocytes, erythrocytes, thrombocytes, and macrophages in diseases, including infectious and inflammatory diseases, cancer, and atherosclerosis, are better understood and have resulted in improved strategies for targeting and in some instances mimicking these cell types to improve therapeutic outcomes. Consequently, these primary cell types can be exploited for the purposes of serving as a “Trojan horse” for targeted delivery to identified organs and sites of inflammation. State of the art and potential utilization of nanocarriers such as nanospheres/nanocapsules, nanocrystals, liposomes, solid lipid nanoparticles/nano-structured lipid carriers, dendrimers, and nanosponges for biomimicry and/or targeted delivery of bioactives to cells are reported herein and their potential use in the treatment of COVID-19 infections discussed. Physicochemical properties, viz., hydrophilicity, particle shape, surface charge, composition, concentration, the use of different target-specific ligands on the surface of carriers, and the impact on carrier efficacy and specificity are also discussed

Impact of the coronavirus disease on the mental health and physical activity of pharmacy students at the University of Zambia: a cross-sectional study

Background: The novel coronavirus disease (COVID-19) is a serious global health problem that has negatively impacted the mental health of students.Methods: We conducted an online descriptive cross-sectional study among 273 undergraduate pharmacy students at the University of Zambia from August to September 2020. A partial proportional odds regression model was used to determine the predictors of anxiety. All statistical tests were set at 95% confidence level (p<0.05).Results: A response rate of 70% was obtained with the majority of the students being female 51.6%. Of the 273 respondents, 23.8% did not experience anxiety, 34.4% experienced mild anxiety, 24.9% experienced moderate anxiety while 16.9% experienced severe anxiety about COVID-19. It was also found that 61.2% of students reported that their attention to mental health increased during the COVID-19 pandemic whereas 44.3% reported an increased resting time with a significant reduction in relaxation 51.3% and physical activity 45.4% time. Factors that affected mental health included; reduced family care (OR: 2.27; 95% CI: 1.09-4.74), not changing attention to mental health (OR: 0.33; 95% CI: 0.18-0.62), being in the final year of study (OR: 0.33; 95% CI: 0.13-0.84), reduced time of resting (OR: 2.10; 95% CI: 1.26-3.50) and feeling helpless (OR: 0.42; 95% CI:0.23-0.75).Conclusions: COVID-19 negatively impacted the mental health and physical activity of pharmacy students at the University of Zambia. This can have negative health and academic outcomes for students going forward. Higher learning institutions and key stakeholders should implement measures to aid students to recover from the impact of COVID-19 on their mental health and physical activity

Impact of the Coronavirus Disease (COVID-19) on the Mental Health and Physical Activity of Pharmacy Students at the University of Zambia: A Cross-Sectional Study.

BACKGROUND: The novel coronavirus disease (COVID-19) is a serious global health problem that has negatively impacted the mental health of students. METHODS: We conducted an online descriptive cross-sectional study among 273 undergraduate pharmacy students at the University of Zambia. A partial proportional odds regression model was used to determine the predictors of anxiety. All statistical tests were set at 95% confidence level (p&lt;0.05). RESULTS: A response rate of 70% was obtained with the majority of the students being female 51.6%. Of the 273 respondents, 23.8% did not experience anxiety, 34.4% experienced mild anxiety, 24.9% experienced moderate anxiety while 16.9% experienced severe anxiety about COVID-19. It was also found that 61.2% of students reported that their attention to mental health increased during the COVID-19 pandemic whereas 44.3% reported an increased resting time with a significant reduction in relaxation 51.3% and physical activity 45.4% time. Factors that affected mental health included; reduced family care (OR: 2.27; 95% CI: 1.09-4.74), not changing attention to mental health (OR: 0.33; 95% CI: 0.18-0.62), being in the final year of study (OR: 0.33; 95% CI: 0.13-0.84), reduced time of resting (OR: 2.10; 95% CI: 1.26-3.50) and feeling helpless (OR: 0.42; 95% CI:0.23-0.75). CONCLUSION: COVID-19 negatively impacted the mental health and physical activity of pharmacy students at the University of Zambia. This can have negative health and academic outcomes for students going forward. Higher learning institutions and key stakeholders should implement measures to aid students to recover from the impact of COVID-19 on their mental health and physical activity