Although disintegration is not always a prerequisite for drug dissolution, this process plays a significant role in the rate and extent of dissolution, especially in the case of sparingly water-soluble drugs (like furosemide). Any factor that influences tablet disintegration, therefore, will influence drug dissolution. Since the filler often comprises more than 80% of the total tablet weight, it will affect tablet properties and therefore disintegration. The solubility of the filler is expected to play a major role in determining tablet disintegration. During the initial stage of the study the physical powder properties (density, particle size, flow properties and compressibility) of Tablettose® (soluble) and Avicel® PH 200 (insoluble) as tablet fillers were determined and compared in order to establish their inherent powder properties. Tablets from mixtures containing each filler and 0.5% w/w magnesium stearate (as lubricant) were prepared at a constant die fill volume at different compression pressures. Since Tablettose® could not be tableted without a lubricant due to high friction during ejection, magnesium stearate was included in all formulations. Tablets were evaluated in terms of weight variation, crushing strength, friability and disintegration times. Tablettose® produced tablets with extremely low crushing strengths and high friability compared to Avicel® PH 200, which produced tablets with - acceptable physical properties. The most significant difference between the two formulations was observed in the disintegration times, with the Avicel® tablets producing rapid disintegration whilst Tablettose® produced slowly dissolving rather than disintegrating tablets. These results indicated shortcomings in the properties of Tablettose® as directly compressible filler and suggested possible problems in terms of drug release. Following the results from the previous experiments, the effect of addition of 3.5, 5 and 7% w/w Kollidon® 30 and Kollidon® VA 64 as dry binder (to increase mechanical strength) and 0.5, 1 and 2% w/w Ac-Di-Sol®, Kollidon® CL and sodium starch glycolate as disintegrant (to induce tablet disintegration) on the physical properties of Tablettose® formulations was evaluated in order to eliminate the observed poor physical tablet properties. Although the presence of a dry binder had little effect on the crushing strength of the tablets it did increase the compression range during tableting, thereby increasing the compression force before capping occurred. Kollidon® VA 64 (3.5%) proved to be the most efficient. The incorporation of a disintegrant, irrespective of the type or concentration of the disintegrant, resulted in a significant decrease in disintegration time (1 % of each disintegrant provided efficient disintegration). This was ascribed to a change from slowly dissolving tablets (with disintegration exceeding 15 minutes) to rapidly disintegrating tablets (with disintegration times less than 3 minutes). In the final stage the dissolution of furosemide (chosen as model drug representing sparingly water-soluble drugs for which dissolution is the rate-limiting step) from Avicel®, Tablettose® and Tablettose®/Kollidon® VA 64 and Ac-Di-Sol®, Kollidon® CL or sodium starch glycolate formulations was determined in 0.1 M HCI. Dissolution results were compared using calculated dissolution parameters, namely the initial dissolution rate (DRi) and the extent of dissolution (AUC). Dissolution from the slowly dissolving Tablettose® tablets was significantly slower compared to the rapid disintegrating Avicel® tablets, confirming the hypothesis that slowly dissolving (but non-disintegrating) formulations impede drug dissolution due to the small surfacearea of the drug exposed to the surrounding medium. The incorporation of Kollidon® VA 64 (as dry binder) in Tablettose® formulations resulted in unexpectedly high drug dissolution comparable with profiles obtained from the Avicel® tablets, despite the fact that the tablets did not disintegrate. The literature provided an answer, indicating that Kollidon® VA 64 increased the solubility of furosemide (Buhler, 1993:114), possibly due to the formation of a drug/excipient complex. Addition of a disintegrant to this formulation further increased drug dissolution due to rapid tablet disintegration. Once again no significant difference in drug dissolution was observed between the three disintegrants used. The dissolution results also indicate a dependency of the extent of drug dissolution (AUC) on the initial dissolution rate (DRi), indicating the importance (although not an absolute prerequisite) of establishment of rapid contact between drug particles and the surrounding medium through the incorporation of a disintegrant. / Thesis (M.Sc.(Pharm.))--Potchefstroom University for Christian Higher Education, 2002

Although disintegration is not always a prerequisite for drug dissolution, this process plays a significant role in the rate and extent of dissolution, especially in the case of sparingly water-soluble drugs (like furosemide). Any factor that influences tablet disintegration, therefore, will influence drug dissolution. Since the filler often comprises more than 80% of the total tablet weight, it will affect tablet properties and therefore disintegration. The solubility of the filler is expected to play a major role in determining tablet disintegration. During the initial stage of the study the physical powder properties (density, particle size, flow properties and compressibility) of Tablettose® (soluble) and Avicel® PH 200 (insoluble) as tablet fillers were determined and compared in order to establish their inherent powder properties. Tablets from mixtures containing each filler and 0.5% w/w magnesium stearate (as lubricant) were prepared at a constant die fill volume at different compression pressures. Since Tablettose® could not be tableted without a lubricant due to high friction during ejection, magnesium stearate was included in all formulations. Tablets were evaluated in terms of weight variation, crushing strength, friability and disintegration times. Tablettose® produced tablets with extremely low crushing strengths and high friability compared to Avicel® PH 200, which produced tablets with - acceptable physical properties. The most significant difference between the two formulations was observed in the disintegration times, with the Avicel® tablets producing rapid disintegration whilst Tablettose® produced slowly dissolving rather than disintegrating tablets. These results indicated shortcomings in the properties of Tablettose® as directly compressible filler and suggested possible problems in terms of drug release. Following the results from the previous experiments, the effect of addition of 3.5, 5 and 7% w/w Kollidon® 30 and Kollidon® VA 64 as dry binder (to increase mechanical strength) and 0.5, 1 and 2% w/w Ac-Di-Sol®, Kollidon® CL and sodium starch glycolate as disintegrant (to induce tablet disintegration) on the physical properties of Tablettose® formulations was evaluated in order to eliminate the observed poor physical tablet properties. Although the presence of a dry binder had little effect on the crushing strength of the tablets it did increase the compression range during tableting, thereby increasing the compression force before capping occurred. Kollidon® VA 64 (3.5%) proved to be the most efficient. The incorporation of a disintegrant, irrespective of the type or concentration of the disintegrant, resulted in a significant decrease in disintegration time (1 % of each disintegrant provided efficient disintegration). This was ascribed to a change from slowly dissolving tablets (with disintegration exceeding 15 minutes) to rapidly disintegrating tablets (with disintegration times less than 3 minutes). In the final stage the dissolution of furosemide (chosen as model drug representing sparingly water-soluble drugs for which dissolution is the rate-limiting step) from Avicel®, Tablettose® and Tablettose®/Kollidon® VA 64 and Ac-Di-Sol®, Kollidon® CL or sodium starch glycolate formulations was determined in 0.1 M HCI. Dissolution results were compared using calculated dissolution parameters, namely the initial dissolution rate (DRi) and the extent of dissolution (AUC). Dissolution from the slowly dissolving Tablettose® tablets was significantly slower compared to the rapid disintegrating Avicel® tablets, confirming the hypothesis that slowly dissolving (but non-disintegrating) formulations impede drug dissolution due to the small surfacearea of the drug exposed to the surrounding medium. The incorporation of Kollidon® VA 64 (as dry binder) in Tablettose® formulations resulted in unexpectedly high drug dissolution comparable with profiles obtained from the Avicel® tablets, despite the fact that the tablets did not disintegrate. The literature provided an answer, indicating that Kollidon® VA 64 increased the solubility of furosemide (Buhler, 1993:114), possibly due to the formation of a drug/excipient complex. Addition of a disintegrant to this formulation further increased drug dissolution due to rapid tablet disintegration. Once again no significant difference in drug dissolution was observed between the three disintegrants used. The dissolution results also indicate a dependency of the extent of drug dissolution (AUC) on the initial dissolution rate (DRi), indicating the importance (although not an absolute prerequisite) of establishment of rapid contact between drug particles and the surrounding medium through the incorporation of a disintegrant. / Thesis (M.Sc.(Pharm.))--Potchefstroom University for Christian Higher Education, 2002

Acquired Immunodeficiency Syndrome (AIDS) is characterized by the progressive destruction of a person’s immune system and is the latest and most serious stage of Human Immunodeficiency Virus (HIV) infection. Botswana currently has the highest estimated prevalence of HIV infection in the world. Botswana has a relatively young population structure, with about 60% of the approximately 1,8 million people aged less than 45 years. HIV prevalence for pregnant women aged 15–45 years in Botswana did, however, decrease marginally from 36,2% in 2001 to 35,4% in 2002. It is estimated that about 258 000 Botswana are now living with HIV and AIDS, and high morbidity and mortality rates due to HIV/AIDS have seen Botswana slip down the United Nations Development Plan (UNDP) Human Development Index rankings from 71 in 1996, to 122 in 1999/2000. In 2002 Botswana initiated public antiretroviral therapy (ART) at four sites initially to provide treatment to HIV/AIDS patients before expanding the programme to the rest of the country. The specific objective of the study was to investigate the prescribing patterns of ARV drugs at Sekgoma Memorial Hospital ARV therapy clinic (SMH–IDCC) in the central district of Botswana for a two–year period from 2005 to 2006. Data from 1717 patients were obtained from the SMH–IDCC electronic database regarding ARV drugs prescribed during the study period, CD4–Tcell count (cells/?L) at the commencement of therapy and after six months from the commencement of therapy and side effects necessitating change of therapy for the study period 2005 until 2006. The study showed that there were eight antiretroviral therapy (ART) regimens prescribed: zidovudine plus lamivudine plus efavirenz (AZT/3TC/EFV), zidovudine plus lamivudine plus nevirapine (AZT/3TC/NVP), Combivir® plus efavirenz (CBV/EFV), Combivir® plus nelfinavir (CBV/NFV), Combivir® plus nevirapine (CBV/NVP), stavudine plus lamivudine plus efavirenz (D4T/3TC/EFV), stavudine plus lamivudine plus nelfinavir (D4T/3TC/NFV), and stavudine plus lamivudine plus nevirapine (D4T/3TC/NVP). The most prescribed ART regimen for adult patients was Combivir® plus efavirenz (CBV/EFV) (51,37%). This was broken down as 17,20% of females and 34,17% of males. The second most prescribed ART regimen was Combivir® plus nevirapine (CBV/NVP)(36% of the total study population (N=1717). This represented 34,17% of females and 1,98% of males. The most prescribed ART regimen in children was zidovudine plus lamivudine plus efavirenz (AZT/3TC/EFV) (3,73% of the total population), broken down as 1,05% of females and 2,68% of males. The second most prescribed regimen in this group was zidovudine plus lamivudine plus nevirapine (ZDV/3TC/NVP) (3,50% of total population). The findings from this study indicated that all eight the ART regimens prescribed at the study site were in accordance with the Botswana national ART guidelines. There were thirteen different types of side effects necessitating change of therapy, including pregnancy, treatment failure and poor adherence. The average CD4–Tcell count change (155.63 cells/?L, ± 204.08 cells/?L) for the study population was more than 100% after six months from commencement of therapy, indicating success of therapy in terms of CD4–Tcell count. / Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2011.

Acquired Immunodeficiency Syndrome (AIDS) is characterized by the progressive destruction of a person’s immune system and is the latest and most serious stage of Human Immunodeficiency Virus (HIV) infection. Botswana currently has the highest estimated prevalence of HIV infection in the world. Botswana has a relatively young population structure, with about 60% of the approximately 1,8 million people aged less than 45 years. HIV prevalence for pregnant women aged 15–45 years in Botswana did, however, decrease marginally from 36,2% in 2001 to 35,4% in 2002. It is estimated that about 258 000 Botswana are now living with HIV and AIDS, and high morbidity and mortality rates due to HIV/AIDS have seen Botswana slip down the United Nations Development Plan (UNDP) Human Development Index rankings from 71 in 1996, to 122 in 1999/2000. In 2002 Botswana initiated public antiretroviral therapy (ART) at four sites initially to provide treatment to HIV/AIDS patients before expanding the programme to the rest of the country. The specific objective of the study was to investigate the prescribing patterns of ARV drugs at Sekgoma Memorial Hospital ARV therapy clinic (SMH–IDCC) in the central district of Botswana for a two–year period from 2005 to 2006. Data from 1717 patients were obtained from the SMH–IDCC electronic database regarding ARV drugs prescribed during the study period, CD4–Tcell count (cells/?L) at the commencement of therapy and after six months from the commencement of therapy and side effects necessitating change of therapy for the study period 2005 until 2006. The study showed that there were eight antiretroviral therapy (ART) regimens prescribed: zidovudine plus lamivudine plus efavirenz (AZT/3TC/EFV), zidovudine plus lamivudine plus nevirapine (AZT/3TC/NVP), Combivir® plus efavirenz (CBV/EFV), Combivir® plus nelfinavir (CBV/NFV), Combivir® plus nevirapine (CBV/NVP), stavudine plus lamivudine plus efavirenz (D4T/3TC/EFV), stavudine plus lamivudine plus nelfinavir (D4T/3TC/NFV), and stavudine plus lamivudine plus nevirapine (D4T/3TC/NVP). The most prescribed ART regimen for adult patients was Combivir® plus efavirenz (CBV/EFV) (51,37%). This was broken down as 17,20% of females and 34,17% of males. The second most prescribed ART regimen was Combivir® plus nevirapine (CBV/NVP)(36% of the total study population (N=1717). This represented 34,17% of females and 1,98% of males. The most prescribed ART regimen in children was zidovudine plus lamivudine plus efavirenz (AZT/3TC/EFV) (3,73% of the total population), broken down as 1,05% of females and 2,68% of males. The second most prescribed regimen in this group was zidovudine plus lamivudine plus nevirapine (ZDV/3TC/NVP) (3,50% of total population). The findings from this study indicated that all eight the ART regimens prescribed at the study site were in accordance with the Botswana national ART guidelines. There were thirteen different types of side effects necessitating change of therapy, including pregnancy, treatment failure and poor adherence. The average CD4–Tcell count change (155.63 cells/?L, ± 204.08 cells/?L) for the study population was more than 100% after six months from commencement of therapy, indicating success of therapy in terms of CD4–Tcell count. / Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2011.

Antiretroviral drugs are successful in controlling HIV/AIDS and reducing disease progression. Antiretroviral regimens are stopped in up to 25% of all patients during their initial treatment therapy as a result of adverse drug effects, failing treatment and nonadherence within the initial eight months of treatment (Sharma et al., 2007: 235). A pharmacovigilance surveillance system makes it possible for physicians, pharmacists and other healthcare providers to report suspected ADRs. The purpose of this system is to operate as a guide in identification of new ADRs and predisposing risk factors to known ADRs. The objective of this study was to assess the prevalence and documentation of adverse drug reactions (ADR) in the private and public antiretroviral clinics in Maseru district, with special reference to zidovudine (AZT) and tenofovir (TDF) - based regimens. The empirical investigation was divided into two phases. The first phase was a cross-sectional quantitative retrospective drug utilisation review study which focused on the occurrence of adverse drug reactions in patients taking zidovudine (AZT) and tenofovir (TDF). The second phase, a survey in a form of questionnaires for the health professionals. Drug utilisation review: The sample size of patients was 300. Of the 44 patients who experience ADRs, 72.73% (n = 32) were female and 27.27% (n = 12) were male. A greater number of patients who experienced ADRs were females with 43.18% (n = 19) presenting with skin rash, 27.27% (n = 12) with nausea/vomiting, and 2.27% (n = 1) with diarrhoea. In male patients, 2.27% (n = 1) had peripheral neuropathy, 18.18% (n = 8) skin rash, 2.27% (n = 1) Fanconi syndrome, 2.27% (n = 1) nausea/vomiting, and 2.27% (n = 1) diarrhoea. Patients whose ART regimen changed due to ADRs were five. 60% (n = 3) of the patients were females and 40% (n = 2) were males. There was an estimated increase of 0.0025 cell/mm³, 0.0026 cell/mm³, 0.0024 cell/mm³, 0.0025 cell/mm³, and of 0.0019 cell/mm³ in CD4 cell count per day according to sex, age group, weight group, initial ART regimen, and ADRs, respectively. An estimated increase of 0.00021 g/dL, 0.00022 g/dL, 0.00018 g/dL, 0.00022 g/dL, and of 0.00020 g/dL in Hb profile per day occurred according to sex, age group, weight group, initial ART regimen, and ADRs, respectively. There was an estimated increase of 0.000062%, 0.000046%, 0.000068%, 0.000062%, and of 0.00017% in neutrophil count according to sex, age group, weight group, initial ART regimen, and ADRs per day, respectively. There was an estimated increase of 0.000044 IU/L, 0.000043 IU/L, 0.000046 IU/L, and of 0.000028 IU/L in ALT according to sex, age group, weight group, and initial ART regimen per day, respectively. An estimated decrease of 0.000013 IU/L in ALT according to ADRs per day also occurred. There was an estimated decrease of 0.00038 μmol/L, 0.00039 μmol/L, 0.00040 μmol/L, 0.00040 μmol/L, and of 0.00028 μmol/L in serum creatinine per day according to sex, age group, weight group, initial ART regimen, and ADRs, respectively. There was an estimated decline of 0.00023 mmol/L, 0.00022 mmol/L, 0.00023 mmol/L, 0.00024 mmol/L, and of 0.00015 mmol/L per day in urea according to sex, age group, weight group, initial ART regimen, and ADRs, respectively. Health professional’s questionnaire: 49 health professionals responded to the questionnaire. 100% (n= 49) of the participants showed that they did not use the yellow card scheme to report ADRs. 34.65% (n = 17) use the individual case safety reports. 57.14% (n = 28) used the structured databases to report ADRs. 85.71% (n = 42) documented in the patient bukana, and 6.12% (n = 3) used the HIV/AIDS ART card to document ADRs occurrence. 91.84% (n = 45) of the health professionals never filled the ADR reporting form in their working environment. In conclusion, adverse drug reactions occurring in a hospital or healthcare facility should be recorded and reported by the medical practitioners, nurses, pharmacists, and the pharmacy technicians. Therefore, it is important to assess the continuous evaluation of the benefits and harm of medicines which will help in achieving the ultimate goal of making safer and more effective treatment available for patients. As well as to help the health professionals to participate in the very important process of continuous surveillance of safety and efficacy of pharmaceutical products used in clinical practice. / MPham (Pharmacy Practice), North-West University, Potchefstroom Campus, 2014

Antiretroviral drugs are successful in controlling HIV/AIDS and reducing disease progression. Antiretroviral regimens are stopped in up to 25% of all patients during their initial treatment therapy as a result of adverse drug effects, failing treatment and nonadherence within the initial eight months of treatment (Sharma et al., 2007: 235). A pharmacovigilance surveillance system makes it possible for physicians, pharmacists and other healthcare providers to report suspected ADRs. The purpose of this system is to operate as a guide in identification of new ADRs and predisposing risk factors to known ADRs. The objective of this study was to assess the prevalence and documentation of adverse drug reactions (ADR) in the private and public antiretroviral clinics in Maseru district, with special reference to zidovudine (AZT) and tenofovir (TDF) - based regimens. The empirical investigation was divided into two phases. The first phase was a cross-sectional quantitative retrospective drug utilisation review study which focused on the occurrence of adverse drug reactions in patients taking zidovudine (AZT) and tenofovir (TDF). The second phase, a survey in a form of questionnaires for the health professionals. Drug utilisation review: The sample size of patients was 300. Of the 44 patients who experience ADRs, 72.73% (n = 32) were female and 27.27% (n = 12) were male. A greater number of patients who experienced ADRs were females with 43.18% (n = 19) presenting with skin rash, 27.27% (n = 12) with nausea/vomiting, and 2.27% (n = 1) with diarrhoea. In male patients, 2.27% (n = 1) had peripheral neuropathy, 18.18% (n = 8) skin rash, 2.27% (n = 1) Fanconi syndrome, 2.27% (n = 1) nausea/vomiting, and 2.27% (n = 1) diarrhoea. Patients whose ART regimen changed due to ADRs were five. 60% (n = 3) of the patients were females and 40% (n = 2) were males. There was an estimated increase of 0.0025 cell/mm³, 0.0026 cell/mm³, 0.0024 cell/mm³, 0.0025 cell/mm³, and of 0.0019 cell/mm³ in CD4 cell count per day according to sex, age group, weight group, initial ART regimen, and ADRs, respectively. An estimated increase of 0.00021 g/dL, 0.00022 g/dL, 0.00018 g/dL, 0.00022 g/dL, and of 0.00020 g/dL in Hb profile per day occurred according to sex, age group, weight group, initial ART regimen, and ADRs, respectively. There was an estimated increase of 0.000062%, 0.000046%, 0.000068%, 0.000062%, and of 0.00017% in neutrophil count according to sex, age group, weight group, initial ART regimen, and ADRs per day, respectively. There was an estimated increase of 0.000044 IU/L, 0.000043 IU/L, 0.000046 IU/L, and of 0.000028 IU/L in ALT according to sex, age group, weight group, and initial ART regimen per day, respectively. An estimated decrease of 0.000013 IU/L in ALT according to ADRs per day also occurred. There was an estimated decrease of 0.00038 μmol/L, 0.00039 μmol/L, 0.00040 μmol/L, 0.00040 μmol/L, and of 0.00028 μmol/L in serum creatinine per day according to sex, age group, weight group, initial ART regimen, and ADRs, respectively. There was an estimated decline of 0.00023 mmol/L, 0.00022 mmol/L, 0.00023 mmol/L, 0.00024 mmol/L, and of 0.00015 mmol/L per day in urea according to sex, age group, weight group, initial ART regimen, and ADRs, respectively. Health professional’s questionnaire: 49 health professionals responded to the questionnaire. 100% (n= 49) of the participants showed that they did not use the yellow card scheme to report ADRs. 34.65% (n = 17) use the individual case safety reports. 57.14% (n = 28) used the structured databases to report ADRs. 85.71% (n = 42) documented in the patient bukana, and 6.12% (n = 3) used the HIV/AIDS ART card to document ADRs occurrence. 91.84% (n = 45) of the health professionals never filled the ADR reporting form in their working environment. In conclusion, adverse drug reactions occurring in a hospital or healthcare facility should be recorded and reported by the medical practitioners, nurses, pharmacists, and the pharmacy technicians. Therefore, it is important to assess the continuous evaluation of the benefits and harm of medicines which will help in achieving the ultimate goal of making safer and more effective treatment available for patients. As well as to help the health professionals to participate in the very important process of continuous surveillance of safety and efficacy of pharmaceutical products used in clinical practice. / MPham (Pharmacy Practice), North-West University, Potchefstroom Campus, 2014