A product must comply with pharmacopeial specifications at all times. If the drug in the tablet degrades to a therapeutically inactive (and sometimes toxic) substance, the patient will not receive the correct amount of drug and, more important, may be adversely affected by the degradation product. The stability characteristics of four products containing either p-aminosalicylic acid or sodium aminosalicylate were, therefore, determined in this laboratory. The products were selected at random and are currently being sold to pharmacies and hospitals in Canada. The products were analyzed and their disintegration times determined. All products complied with existing specifications. The products were then stored in a Vapor-Temp Controlled Humidity Chamber at various temperatures (30°C. to 60°C.) and at 65 % and 90 % relative humidity for varying periods of time. Tablets were withdrawn from the chamber at various times and analyzed. Using the data so obtained, rate constants were calculated for each product stored at the two basic conditions, that is, at 65 % and 90 % relative humidity. Products 1 and 4 were not affected by the environmental conditions in the humidity chamber. However, the drug in Products 5 and 7 degraded quickly to m-aminophenol when the tablets were exposed to temperatures in excess of 40°C and a relative humidity of 90 %. Product 7, in particular, was very susceptible to both heat and moisture. The product would, therefore, be unacceptable to the profession. It contains buffers and it is assumed that these substances are responsible for the product's instability. This then is a good example of poor product development. The data accumulated during this investigation was analyzed mathematically and it was concluded that the pseudo first-order reaction equation may be used to explain the degradation process. Arrhenius plots (that is, plots of the logarithm of the rate constant versus the reciprocal of the absolute temperature) were prepared for Products 5 and 7. On the basis of these plots, product stability at various temperatures and a relative humidity of 90 % was determined. As an example, Product 7 will contain only 90% of the drug claimed on the label if it is stored at a temperature of 25°C and a relative humidity of 90% for 70 days. Values at other temperatures and for Product 5 are given in this thesis. The data obtained during this investigation suggests that the following stability specification may be used to quickly evaluate a product containing p-Aminosalicylic acid or its sodium salt. Place 20 tablets in a petrie dish and transfer to a humidity chamber adjusted to 40°C and a relative humidity of 90%. Store in the chamber for ten days. Remove and assay the tablets. The mean potency of the 20 tablets must be not less than 90 % of the amount claimed on the label. The drug in products which do not meet this specification would degrade to m-aminophenol even if it is stored at normal temperatures for relatively short periods of time. Product 7 falls into this category. This study shows that humidity must be taken into consideration in any investigation on product stability. Moreover, it is not enough to determine the stability of the drug as such. The excipients (and other drugs combined with the anti-tubercular in the same dosage form) can influence the degradation process in the tablet. This abstract represents the true contents of the thesis submitted. / Pharmaceutical Sciences, Faculty of / Graduate

Pyomyositis is a severe bacterial infection of skeletal muscle, commonly affecting children in tropical regions, predominantly caused by Staphylococcus aureus. To understand the contribution of bacterial genomic factors to pyomyositis, we conducted a genome-wide association study of S. aureus cultured from 101 children with pyomyositis and 417 children with asymptomatic nasal carriage attending the Angkor Hospital for Children, Cambodia. We found a strong relationship between bacterial genetic variation and pyomyositis, with estimated heritability 63.8% (95% CI 49.2-78.4%). The presence of the Panton-Valentine leucocidin (PVL) locus increased the odds of pyomyositis 130-fold (p=10- 17.9 ). The signal of association mapped both to the PVL-coding sequence and the sequence immediately upstream. Together these regions explained over 99.9% of heritability (95% CI 93.5-100%). Our results establish staphylococcal pyomyositis, like tetanus and diphtheria, as critically dependent on a single toxin and demonstrate the potential for association studies to identify specific bacterial genes promoting severe human disease.

Polymer based nanoparticle formulations have been shown to increase drug bioavailability and/or reduce drug adverse effects. Nonsteroidal anti-inflammatory drugs (e.g. celecoxib) reduce prostaglandin synthesis and cause side effects such as gastrointestinal and renal complications. The aim of this study was to formulate celecoxib entrapped poly lactide-co-glycolide based nanoparticles through a solvent evaporation process using didodecyldimethylammonium bromide or poly vinyl alcohol as stabilizer. Nanoparticles were characterized for zeta potential, particle size, entrapment efficiency, and morphology. Effects of stabilizer concentration (0.1, 0.25, 0.5, and 1% w/v), drug amount (5, 10, 15, and 20 mg), and emulsifier (lecithin) on nanoparticle characterization were examined for formula optimization. The use of 0.1, 0.25, and 0.5% w/v didodecyldimethylammonium bromide resulted in a more than 5-fold increase in zeta potential and a more than 1.5-fold increase in entrapment efficiency with a reduction in particle size over 35%, when compared to stabilizer free formulation. Nanoparticle formulations were also highly influenced by emulsifier and drug amount. Using 0.25% w/v didodecyldimethylammonium bromide NP formulations, peak zeta potential was achieved using 15 mg celecoxib with emulsifier (17.15±0.36 mV) and 20 mg celecoxib without emulsifier (25.00±0.18 mV). Peak NP size reduction and entrapment efficiency was achieved using 5 mg celecoxib formulations with (70.87±1.24 nm and 95.55±0.66%, respectively) and without (92.97 ±0.51 nm and 95.93±0.27%, respectively) emulsifier. In conclusion, formulations using 5 mg celecoxib with 0.25% w/v didodecyldimethylammonium bromide concentrations produced nanoparticles exhibiting enhanced size reduction and entrapment efficiency. Furthermore, emulsifier free formulations demonstrated improved zeta potential when compared to formulations containing emulsifier (p<0.01). Therefore, our results suggest the use of emulsifier free 5 mg celecoxib drug formulationscontaining 0.25% w/v didodecyldimethylammonium bromide for production of polymeric NPs that demonstrate enhanced zeta potential, small particle size, and high entrapment efficiency

Most antiepileptic drugs (AEDs) cause some degree of adverse drug reactions. Behavioral side effects (BSEs) associated with AEDs are often overlooked, but are a significant consideration. Agitation, aggression, psychosis, behavioral disorders, hyperactivity, and restlessness are some AED-related BSEs. Contributing causes may include pharmacologic activity, forced normalization, patient characteristics, individual susceptibility, and medication parameters such as dosage and drug interactions. The pharmacist must educate the patient and caregivers about possible BSEs in order to minimize the impact of behavioral changes and improve quality of life.

Non-steroidal anti-inflammatory drugs (NSAIDs) are used chronically to reduce pain and inflammation in patients with arthritic conditions, and also acutely as analgesics by many patients. Both therapeutic and adverse effects of NSAIDs are due to inhibition of cyclooxygenase (COX) enzyme. NSAIDs are classified as non-selective and COX-2-selective inhibitors (COXIBS) based on their extent of selectivity for COX inhibition. However, regardless of their COX selectivity, reports are still appearing on the GI side effect of NSAIDs particularly on the lower gastrointestinal (GI) tract and the harmful role of their controlled release formulations. In addition, previously unpublished data stored in the sponsor's files, question the GI sparing properties of rofecoxib, a COXIB that has been withdrawn due to cardiovascular (CV) side effects. Presently, the major side effects of NSAIDs are the GI complications, renal disturbances and CV events. There is a tendency to believe that all NSAIDs are associated with renal and CV side effects, a belief that is not supported by solid evidence. Indeed, lower but still therapeutics doses of some NSAIDs may be cardioprotective. In this review, we briefly discuss the GI toxicity of the NSAIDs and assess their renal and CV adverse effects in more detail.

Disability and health care-related costs continue to rise as a result of work-related low back injury. Our investigation examined treatment-independent variables that influenced return-to-work outcome in a sample of workers employed in Northeast Tennessee. METHODS: The review collected 11 variables from two different outpatient physical therapy clinics utilizing a balanced quota sampling design. The patients were enrolled if the documented complaint was low back pain and was an employment-related injury. The patients were grouped according to whether or not they returned to full-time pre-injury work. Twenty-five patients were enrolled in the positive outcome group, those who returned to full-time pre-injury work. Twenty-two patients who did not achieve this goal were enrolled in a separate group. RESULTS: Return-to-work for these patients was not dependent upon age, gender, insurer, number of physical therapy treatments attended, or previously reported low back injury. Those who returned to work had (1) a higher percentage of patients working full-time at their pre-injury position during the rehabilitation process (28% vs. 0%); (2) a higher compliance with the treatment schedule (97% vs. 93%); (3) a lower cancellation rate (0.5 vs. 2.4); (4) a shorter interval in days between reporting the injury and initiation of physical therapy rehabilitation (27 vs. 58); and (5) a lower percentage of previous surgeries resulting from low back injuries (12% vs. 36%), than those who did not. A relationship was also demonstrated between previous surgery and the interval prior to beginning treatments (P < or = 0.0001). However, no relationship was observed between previous surgery and compliance, or between the interval prior to beginning treatments and compliance. DISCUSSION: These results document two variables representing independent factors affecting return-to-work in this population. The first was previous injury influencing the current injury, as documented by both previous surgery and the interval between the current injury and beginning of treatments. The second was compliance with the treatment schedule for the current injury. The psychosocioeconomic aspects of these results are discussed.

Most antiepileptic drugs (AEDs) cause some degree of adverse drug reactions. Behavioral side effects (BSEs) associated with AEDs are often overlooked, but are a significant consideration. Agitation, aggression, psychosis, behavioral disorders, hyperactivity, and restlessness are some AED-related BSEs. Contributing causes may include pharmacologic activity, forced normalization, patient characteristics, individual susceptibility, and medication parameters such as dosage and drug interactions. The pharmacist must educate the patient and caregivers about possible BSEs in order to minimize the impact of behavioral changes and improve quality of life.

Non-steroidal anti-inflammatory drugs (NSAIDs) are used chronically to reduce pain and inflammation in patients with arthritic conditions, and also acutely as analgesics by many patients. Both therapeutic and adverse effects of NSAIDs are due to inhibition of cyclooxygenase (COX) enzyme. NSAIDs are classified as non-selective and COX-2-selective inhibitors (COXIBS) based on their extent of selectivity for COX inhibition. However, regardless of their COX selectivity, reports are still appearing on the GI side effect of NSAIDs particularly on the lower gastrointestinal (GI) tract and the harmful role of their controlled release formulations. In addition, previously unpublished data stored in the sponsor's files, question the GI sparing properties of rofecoxib, a COXIB that has been withdrawn due to cardiovascular (CV) side effects. Presently, the major side effects of NSAIDs are the GI complications, renal disturbances and CV events. There is a tendency to believe that all NSAIDs are associated with renal and CV side effects, a belief that is not supported by solid evidence. Indeed, lower but still therapeutics doses of some NSAIDs may be cardioprotective. In this review, we briefly discuss the GI toxicity of the NSAIDs and assess their renal and CV adverse effects in more detail.

No description available.

No description available.