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Preparation, characterization and optimization of carbamazepine based pellets prepared by extrusion-spheronization technique

Medicine use in swallowing-impaired patients: Pharmacists’ knowledge, practice and information needs

  • Authors: Masilamoney, Mehrusha
  • Date: 2018
  • Subjects: Deglutition disorders , Drugs -- Administration , Oral medication -- Administration , Pharmacists -- Practice , South African Pharmacy Council
  • Language: English
  • Type: text , Thesis , Masters , MPharm
  • Identifier: http://hdl.handle.net/10962/61940 , vital:28086
  • Description: Dysphagia, or swallowing impairment, is a growing problem that affects 13.5% of the general population. The ability to swallow is essential for patients taking oral medicines, so this presents a challenge for swallowing-impaired (SI) patients as tablets and capsules will usually require modification prior to ingestion. Pharmacists should play a central role in advising SI patients about their medicine use, as well as problems that may impact on safety, adherence and therapeutic outcome. However, little is known about pharmacists’ level of knowledge, their practice and their information needs when dealing with SI patients and their use of medicines. The aim of this study was to investigate pharmacist knowledge, practice and information needs relating to the support of SI patients and their medicine-related needs. The study design included both quantitative and qualitative methods. A quantitative questionnaire was developed to collect data on the knowledge, practice and information needs of pharmacists and was piloted in 10 pharmacists, which resulted in minor modifications. The questionnaire was converted to a web-based survey and emailed to all pharmacists registered with the South African Pharmacy Council. Two knowledge scores were generated by summating correct responses: knowledge of dysphagia (KOD) and knowledge of medicine use (KOMU) in SI patients. Correlation analysis was used to investigate the strength of the relationship between specific variables with KOD and KOMU using the Pearson correlation coefficient. Qualitative semi-structured interviews were conducted with pharmacists from community, hospital and primary healthcare clinics in both a small town and a major metropole. The aim was to gain deeper understanding of issues arising from the survey, and to explore preferences for topic-specific information materials. All interviews were audio-recorded and transcribed verbatim. Thematic analysis was used to analyse the data. A total of 439 pharmacists responded to the survey, with 67% being females.The mean KOD score out of a maximum score of 10 was 6.1 ± 1.8. KOD was inadequate (<5) in just over one-third (37.8%) of pharmacists. The mean KOMU score achieved (maximum score 17) was 9.4 ± 2.0, with inadequate knowledge (<10) being established in just over two-thirds of pharmacists (70.8%). Age, length of registration as a pharmacist, and years of practice in a setting with direct patient interaction were significantly but weakly correlated with KOMU, whereas KOD showed no significant association with these variables. Qualification significantly influenced both KOD and KOMU; the highest group with adequate knowledge had either a Masters or a PharmD degree. Fewer than half the pharmacists (44%) never ask patients about their swallowing ability, and most (86%) reported no knowledge of locally available viscosity enhancers. Almost all pharmacists were interested in receiving information materials on assisting SI patients with their medicine use. Three major themes emerged from the semi-structured interviews. Pharmacists recognised their knowledge deficit and felt that lack of both undergraduate training and formal training during practice, as well as limited exposure to SI patients, were contributing factors. Barriers to their practice with SI patients included lack of time, lack of institutional support and lack of easily accessible references on the pharmacists’ role in supporting medicine use in SI patients. Lastly, most pharmacists were not prepared to take ownership of medicine-related problems in SI patients and had conflicting opinions of the pharmacists’ role, usually shifting the responsibility of medicine use in SI patients to nurses. This is the first study to investigate pharmacist knowledge of medicine use in SI patients. The findings indicate that pharmacists do not have the requisite knowledge when dealing with SI patients and their medicine-taking issues despite being the most highly trained healthcare professionals in this field. Lack of undergraduate training, in-house training and limited exposure to SI patients were reported to contribute to poor knowledge. Current practice revealed that there appears to be poor communication among different healthcare professionals, pharmacists were reluctant to work with and/or train nurses on appropriate medicine use in SI patients, and there appeared to be ambiguity surrounding the role of a pharmacist. This research identified that pharmacists regard this topic to be highly relevant to their everyday practice and are keen to receive more information and training relating to this area of study. Information materials were designed and will be made accessible to all pharmacists registered in South Africa.
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  • Date Issued: 2018

Comparison of the neuroprotective potential of theanine and minocycline

  • Authors: Mpofu, Tariro Ann-Maureen
  • Date: 2010 , 2010-09-20
  • Subjects: Nervous system -- Degeneration -- Treatment , Tetracyclines , Antibiotics -- Side effects , Theanine -- Evaluation , Drugs -- Administration , Cerebrovascular disease -- Prevention
  • Language: English
  • Type: Thesis , Masters , MSc
  • Identifier: vital:3775 , http://hdl.handle.net/10962/d1003253 , Nervous system -- Degeneration -- Treatment , Tetracyclines , Antibiotics -- Side effects , Theanine -- Evaluation , Drugs -- Administration , Cerebrovascular disease -- Prevention
  • Description: Stroke is one of the most common causes of disability and death worldwide. The most commonly experienced stroke in the clinical setting is focal ischaemia in which the middle cerebral artery (MCA) is occluded and leads to a complex series of various pathophysiological pathways that ultimately lead to neuronal cell death. Several studies have been conducted on various therapeutic agents in the search for a neuroprotective drug and various animal models have been used to carry out this research. While theanine, a component of green tea and minocycline, a tetracycline antibiotic, have been shown to possess some neuroprotective properties, the mechanisms by which these two agents carry out these effects still remains unclear. The objectives of this study were to investigate the mechanisms by which these drugs carry out these neuroprotective effects and their neuroprotective ability in a MCA occlusion model of focal ischaemia. Ischaemia leads to oxidative stress due to the imbalance of free radicals and the endogenous antioxidant defence system. An antioxidant assay using the stable 2, 2-diphenyl-1-picrylhydrazyl (DPPH●) radical was used to assess the antiradical properties of each drug. It was found that minocycline showed superior antioxidant activity in vitro when compared to theanine. Further studies on the drugs‟ ability to attenuate the Fenton reaction (in which iron catalyses the formation of reactive species) were elucidated using electrochemical analysis, UV/VIS studies, ferrozine and ferritin assays. It was found that minocycline, in contrast to theanine, was able to bind to iron ions and thus potentially prevent the participation of iron in metal catalysed radical reaction. The antioxidant activity of both drugs was further investigated by assessing their effect on cyanide-induced superoxide generation and quinolinic acid (QA)-induced lipid peroxidation (LP). Experimental evidence shows that both drugs had no significant effect on the generation of superoxide in vitro and that there was a significant decrease in LP for minocycline in vitro and theanine in vivo. The metal binding and antioxidant properties were postulated to be a possible mechanism through which these agents reduced lipid peroxidation. A study was conducted to determine the effects of the drugs on the biosynthesis of the neurotoxin, QA and it was found that minocycline increases the levels of holoenzyme activity of tryptophan-2, 3-dioxygenase (TDO) in vitro and that theanine reduces the levels of the same enzyme in vivo after treatment for 10 days. TDO is the enzyme that converts tryptophan to other products that enable enzymatic activity to change it to QA. Minocycline was thought to bring about this effect as it has been shown from preceding experimental studies that it is an effective reducing agent. Theanine on the other hand is hypothesised to bring about a reduction in holoenzyme activity by changing the binding of tryptophan to the enzyme or affecting the radicals that participate in the enzymatic degradation of tryptophan. A focal ischaemic model of stroke was induced by occluding the MCA. Histological examination of the hippocampus post -ischaemia shows a reduction in the size of the infarct after pre-treatment with minocycline only. A further study into the effects of the drugs on the generation of superoxide and on the levels of the endogenous glutathione after a stroke was carried out. Pre-treatment of the animals with either theanine or minocycline showed no significant effects on the generation of the radical species or of the endogenous antioxidant which ruled out these as a mechanism of neuroprotection of both drugs, post-ischaemia.The findings of this study provide novel information on the possible mechanisms by which both theanine and minocycline act to bring about neuroprotection. In particular in this study, pre-treatment with minocycline has shown promise in the focal ischaemic model of stroke.
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  • Date Issued: 2010

Development and assessment of minocycline sustained release capsule formulations

  • Authors: Sachikonye, Tinotenda Chipo Victoria
  • Date: 2010
  • Subjects: Drugs -- Controlled release , Drugs -- Dosage forms , Capsules (Pharmacy) , Drugs -- Administration , Acne -- Treatment , Tetracyclines , Antibiotics -- Side effects
  • Language: English
  • Type: Thesis , Masters , MSc
  • Identifier: vital:3854 , http://hdl.handle.net/10962/d1013127
  • Description: The use of minocycline for the treatment of a broad range of systemic infections and for severe acne has been associated with vestibular side effects. The severity of side effects may lead to poor adherence to therapy by patients. The use of sustained release formulations of minocycline that display slow dissolution of minocycline following administration may be beneficial in reducing the incidence and severity of side effects. Therefore, sustained release capsule dosage forms containing 100 mg minocycline (base) were manufactured and assessed for use as sustained release oral dosage forms of minocycline. Minocycline sustained release capsules were manufactured based on matrix technologies using hydroxypropylmethyl cellulose (HPMC) and Compritol® as release retarding polymers. The rate and extent of minocycline release from the capsules was evaluated using USP Apparatus 1 and samples were analysed using a validated High Performance Liquid Chromatographic (HPLC) method with ultraviolet (UV) detection. Differences in the rate and extent of minocycline release from formulations manufactured using HPMC or Compritol® were influenced by the concentration of polymer used in the formulations. The rate and extent of minocycline release was faster and greater when low concentrations of polymer were used in formulations. The effect of different excipients on the release pattern(s) of minocycline and particularly their potential to optimise minocycline release from experimental formulations was investigated. The use of diluents such as lactose and microcrystalline cellulose (MCC) revealed that lactose facilitated minocycline release when HPMC was used as the polymer matrix. In contrast, the use of lactose as diluent resulted in slower release of minocycline from Compritol® based formulations. The addition of sodium starch glycolate to HPMC based formulations resulted in slower release of minocycline than when no sodium starch glycolate was used. Compritol® based formulations were observed to release minocycline faster following addition of sodium starch glycolate and Poloxamer 188 to experimental formulations. In vitro dissolution profiles were compared to a target or reference profile using the difference and similarity factors, ƒ1 and ƒ2 , and a one way analysis of variance (ANOVA). In addition, the mechanism of minocycline release was elucidated following fitting of dissolution data to the Korsmeyer-Peppas, Higuchi and Zero order models. Minocycline release kinetics were best described by the Korsmeyer-Peppas model and the values of the release exponent, n (italics), revealed that drug release was a result of the combined effects of minocycline diffusion through matrices and erosion of the matrices. These in vitro dissolution profiles were better fit to the Higuchi model than to the Zero order model. Two formulations that displayed a fit to the Zero order model were identified for further studies as potential dosage forms for sustained release minocycline.
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  • Date Issued: 2010

Formulation and assessment of verapamil sustained release tablets

  • Authors: Khamanga, Sandile Maswazi Malungelo
  • Date: 2005
  • Subjects: Verapamil , Tablets (Medicine) , Drugs -- Administration , Cardiovascular agents , Calcium -- Antagonists , Drugs -- Controlled release
  • Language: English
  • Type: Thesis , Masters , MSc
  • Identifier: vital:3869 , http://hdl.handle.net/10962/d1018236
  • Description: The oral route of drug administration is most extensively used due to the obvious ease of administration. Verapamil hydrochloride is a WHO listed phenylalkylarnine, L-type calcium channel antagonist that is mainly indicated for cardiovascular disorders such as angina pectoris, supraventricular tachycardia and hypertension. Due to its relatively short half-life of approximately 4.0 hours, the formulation of a sustained-release dosage form is useful to improve patient compliance and to achieve predictable and optimized therapeutic plasma concentrations. Direct compression and wet granulation were initially used as methods for tablet manufacture. The direct compression method of manufacture produced tablets that exhibited formulation and manufacturing difficulties. Mini-tablets containing veraparnil hydrochloride were then prepared by wet granulation using Surelease® E-7-19010.and Eudragit® NE 30D as the granulating agents after which the granules were incorporated with an hydrophilic matrix material, Carbopol® 974P NF. Granule and powder blends were evaluated using the angle of repose, loose and tapped bulk density, Can's compressibility index, Hausner's ratio and drug content. Granules with good flow properties and satisfactory compressibility were used for further studies. Tablets were subjected to thickness, diameter and weight variation tests, crushing strength, tensile strength, friability and content uniformity studies. Tablets that showed acceptable pharmaco-technical properties were selected for further analysis. Drug content uniformity and dissolution release rates were determined using a validated isocratic HPLC method. Initially, USP apparatus 1 and 3 dissolution apparatus were used to determine in-vitro drug release rates from the formulations over a 22-hour period. USP apparatus 3 was finally selected as it offers the advantages of mimicking, in part, the changes in the physicochemical environment experienced by products in the gastro-intestinal tract. Differences in release rates between the test formulations and a commercially available product, Isoptin® SR were observed at different pH's using USP apparatus 1. The release of veraparnil hydrochloride from matrix tablets was pH dependent and was markedly reduced at higher pH values. This may be due, in part, to the poor solubility of veraparnil hydrochloride at these pH values and also the possible interaction of verapamil hydrochloride with anionic polymers used in these formulations. Swelling and erosion behaviour of the tablets were evaluated and differences in behaviour were observed which may be attributed to the physico-chemical characteristics of the polymers used in this study. In-vitro dissolution profiles were characterized by the difference (j1) and similarity factor (j2) and also by a new similarity factor, Sct. In addition, the mechanism of drug release from these dosage forms was mainly evaluated using the Korsmeyer-Peppas model and the kinetics of drug release assessed using other models, including Zero order, First order, Higuchi, HixsonCrowell, Weibull and the Baker-Lonsdale model. Dissolution kinetics were best described by application of the Weibull model, and the Korsmeyer-Peppas model. The release exponent, n, confirmed that drug release from these dosage forms was due to the mixed effects of diffusion and swelling and therefore, anomalous release kinetics are predominant. In conclusion, two test batches were found to be comparable to the reference product Isoptin® SR with respect to their in-vitro release profiles.
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  • Date Issued: 2005

Formulation and assessment of monolithic beta blocker sustained release tablets prepared by direct compression

  • Authors: Kieser, Leith Faye
  • Date: 2002
  • Subjects: Drugs -- Dosage forms , Drugs -- Administration , Pharmacology, Experimental , Adrenergic beta blockers , Tablets (Medicine) , Tableting , Neuropharmacology
  • Language: English
  • Type: Thesis , Masters , MSc
  • Identifier: vital:3764 , http://hdl.handle.net/10962/d1003242 , Drugs -- Dosage forms , Drugs -- Administration , Pharmacology, Experimental , Adrenergic beta blockers , Tablets (Medicine) , Tableting , Neuropharmacology
  • Description: Beta blockers are commonly prescribed for the chronic treatment of hypertension, one of the most prolific disease states worldwide. The beta blockers selected for this study include acebutolol hydrochloride, labetalol hydrochloride, metoprolol tartrate oxprenolol hydrochloride and propranolol hydrochloride. All of these compounds have a short elimination half-life, necessitating multiple dose per day regimens and therefore the development of sustained release dosage forms incorporating these agents was considered beneficial in terms of extending the dosing interval, with the aim of improving patient compliance and subsequent therapeutic outcomes. Preformulation studies that were conducted included moisture content analysis by Karl Fischer titration, and DSC, a method used to predict potential interactions between the drugs and tablet excipients. Tablets were manufactured by both wet granulation and direct compression techniques, and the resultant drug release characteristics were evaluated using the USP Apparatus 3(BIO.DIS). A validated isocratic HPLC method, capable of separating the five drug candidates simultaneously, was developed and used for the analysis of drug samples. Tablet quality was assessed using analyses that included the physical assessment of weight, diameter, thickness, hardness and friability, as well as content uniformity of tablets, before and after dissolution testing. Direct compression tablet formulations containing each of the five beta blockers were successfully adapted from a prototype wet granulation matrix tablet containing metoprolol tartrate, and various formulation variables were investigated to establish,their effect on the rate and extent of drug release from these tablets. The grade and quantity of ethylcellulose used in the wet granulation and direct compression formulae influenced the release rate of some drug candidates. In addition, an alternative formulation method, involving freeze-drying of the drug with an ethylcellulose dispersion, was shown to have potential for altering release rates further. Anti-frictional agents, talc and colloidal silicon dioxide, did not affect drug release from these matrices,however, they affected the physical character:istics such as tablet weight and thickness, of the resultant tablets. All of the matrix tablets formulated were shown to release drug according to square root of time kinetics, in a sustained manner over a 22 hour period.
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  • Date Issued: 2002

Design, development and evaluation of encapsulated oral controlled release theophylline mini-tablets

  • Authors: Munday, Dale Leslie
  • Date: 1991
  • Subjects: Drugs -- Administration , Drugs -- Bioavailability , Drugs -- Controlled release , Drugs -- Dosage forms , Tablets (Medicine) , Biopharmaceutics , Drugs -- Testing
  • Language: English
  • Type: Thesis , Doctoral , PhD
  • Identifier: vital:3777 , http://hdl.handle.net/10962/d1003255 , Drugs -- Administration , Drugs -- Bioavailability , Drugs -- Controlled release , Drugs -- Dosage forms , Tablets (Medicine) , Biopharmaceutics , Drugs -- Testing
  • Description: Conventional solid dosage forms often lead to fluctuations which exceed the maximum safe therapeutic level and/or decline below the minimum effective level. It is recognised that many drugs for chronic administration should be administered on a schedule that maintains plasma drug concentration within the therapeutic window. Research in controlled release dosage forms aims at designing a system with a zero-order input (eg, ideally to deliver 8.33% of the dose per hour over a 12 hour duration), producing steady state plasma drug levels. Oral dministration of drugs prepared as a controlled release formulation is extremely popular, and has attracted the attention of pharmaceutical scientists during the last decade. This has been due to the simultaneous convergence of various factors (eg, discovery of novel polymers and devices, better understanding of formulation and physiological constraints, expiration of existing patents, prohibitive cost of developing new drug entities), involved in the development of these delivery systems. Controlled release oral products can be formulated as single or multiple unit dosage forms and the relative merits of multiple unit forms with their own rate controlling systems are well established. This work describes the development of a relatively inexpensive multiple-unit capsule dosage form of theophylline containing coated mini-tablets for drug delivery throughout the gastrointestinal tract. Preformulation studies on theophylline anhydrous included solubility and dissolution rate determinations. Techniques including X-ray powder diffraction, differential scanning colorimetry and infrared spectroscopy provided no evidence of true polymorphism after recrystallisation from various solvents. However, scanning electron micrographs showed the effects of solvent polarity and cooling rate on the size and shape of recrystallised particles. Theophylline granules were manufactured by using various binders and were film coated by fluidised bed technology with various proportions of ethylcellulose, containing varying amounts of PEG 1540. In vitro release rates were dependent upon coating thickness and the proportion of PEG, which, being water soluble, created pores in the coating during dissolution studies as observed by a scanning electron microscope. However, substantial proportions of the drug remained unreleased from the granules. In order to overcome the problems of drug retention, plain granules were used and theophylline mini-tablets (3 mm diameter, weighing 15 - 20 mg) were manufactured and film coated with various Eudragits ® and other polymeric mixtures (soluble and insoluble). In vitro dissolution profiles from samples enclosed in hard gelatin capsules were determined using the USPXXI paddle apparatus in test media at pH 1.2 (HCI), pH 5.4 and 7.4 (phosphate buffers) at 37'C. Monitoring of in vitro theophylline release over 12 h, under identical hydrodynamic conditions, showed that the dissolution rate at pH 1.2 is substantially greater (95% of total drug content released in < 10 h) than that in phosphate buffers. The maximum release after 12 h was approximately 20 and 30% of total drug content of the tablet at pH 5.4 and 7.4, respectively. However, in vivo bioavailability after oral administration of tablets to rabbits corresponded to over 95% of total drug, compared with the same dose administered intravenously. The retarded drug release during in vitro dissolution in phosphate buffer was attributed to a possible interaction of phosphate ions with theophylline molecules at the tablet core-coat interface. These findings indicate that both rate and extent of theophylline release from the slow release coated mini-tablets are highly sensitive to phosphate buffers. The data also emphasise the usefulness of an animal model for assessment of in vivo drug release and subsequent absorption during the development of modified release dosage forms. Mini-tablets were subjected to isothermal and cyclic stresses to reach conditions for up to 6 months at different temperatures and relative humidity. The film integrity was maintained but ageing of the coating occurred which impeded dissolution. Reduced drug release was temperature related while the effect of relative humidi% was insignific~t. Encapsulated mini-tablets (uncoated and coated with Eudragit RL and RS 2% w/w) equivalent to a 300 mg dose, were evaluated both in vitro and in vivo using beagle dogs. The pharmacokinetic parameters from single and multiple dose studies showed several advantages over Theo-Dur® 300 mg tablets. Precise dosage titration is possible by careful adjustment of the number of encapsulated mini-tablets. This multiple unit mini-tablet delivery system will allow for greater flexibility in dosage adjustment compared to the currently available preparations, allowing individualised fine dose titration in those patients requiring therapeutic drug monitoring. The developmentof the multiple unit mini-tablet formulation appears to provide an optimal dosage form with maximum flexibility in respect of dose, duration range and ease of production.
  • Full Text:
  • Date Issued: 1991
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