Tablet Formulation of a Synthesized Celecoxib Potassium Salt and Development of a Validated Method for Its Analysis.

BACKGROUND: Celecoxib is a non-steroidal anti-inflammatory drug (NSAID) and cyclooxygenase-2 (COX-2) inhibitor. It is used for the treatment of rheumatoid arthritis, osteoarthritis, juvenile arthritis, and acute pain. Celecoxib has low systemic bioavailability due to its low water solubility. This study aimed to improve water solubility and dissolution profile by synthesizing a suitable celecoxib potassium salt (celecoxib-K salt). METHODS: Four celecoxib salts were synthesized, and the solubility of these four salts was determined. Celecoxib- K monohydrate salt was chosen for tablet formulation. A simple and feasible reversed-phase high-performance liquid chromatography (HPLC) method was developed for the analysis of the formulated tablet and then validated according to international guidelines. The dissolution profile, shelf life, and accelerated stability studies on the formulated tablet were conducted. RESULTS: Celecoxib-K monohydrate salt exhibited increased water solubility by more than 140-folds (0.464 mg/ml) compared with celecoxib. The in vitro dissolution profile of the formulated celecoxib-K salt tablet was totally dissolved after 10 min. The developed analytical HPLC method was a reliable and valid method with good linearity, accuracy, and precision. Moreover, it was sensitive, and the limit of detection and quantification (LOD and LOQ) were 0.001 and 0.1 mg/L, respectively. The formulated celecoxib-K monohydrate salt tablet was stable under room temperature and accelerated condition for 60 days. CONCLUSION: The potassium salt of celecoxib was highly increased, and the formulated tablet of celecoxib-K salt exhibited a good dissolution profile in the water. In addition, the developed HPLC method was valid and reliable for the analysis and quantification of the formulated tablet. The formulated tablet was stable both at room temperature and under stress conditions.

Evaluation of food effect on the oral absorption of clarithromycin from immediate release tablet using physiological modelling.

BACKGROUND: Food may affect the oral absorption of drugs. PURPOSE: The aim of the present study was to investigate the influence of food on the oral absorption of clarithromycin by evaluating the effect of media parameters, such as pH, bile secretions and food composition, on the release of the drug from immediate release tablets, using in vitro and in silico assessments. METHOD: The solubility, disintegration and dissolution profiles of clarithromycin 500 mg immediate release tablets in compendial media with/without the addition of a homogenized FDA meal as well as in biorelevant simulated intestinal media mimicking fasting and fed conditions were determined. These in vitro data were input to GastroPlus™, which was used for developing a physiological absorption model capable of anticipating the effect of food on clarithromycin absorption. Level A in vitro-in vivo linear correlations were established using a mechanistic absorption modelling based deconvolution approach. RESULTS: The pH of the media has a profound effect on clarithromycin solubility, tablet disintegration and drug release. Clarithromycin has lower solubility in biorelevant media compared with other media, due to complex formation with bile salts. Clarithromycin tablets exhibited prolonged disintegration times and reduced dissolution rates in the presence of the standard FDA meal. The simulation model predicted no significant food effect on the oral bioavailability of clarithromycin. The developed IVIVC model considered SIF, acetate buffer and FaSSIF media to be the most relevant from the physiological standpoint. CONCLUSION: The intake of a standard FDA meal may have no significant effect on the oral bioavailability of clarithromycin immediate release tablet.

Bibliometric analysis of global publications in medication adherence (1900-2017).

OBJECTIVES: Medication non-adherence is a worldwide problem. The aim of this study was to assess the global research output, research trends and topics that shaped medication adherence research. METHODS: A bibliometric methodology was applied. Keywords related to 'medication adherence' were searched in Scopus database for all times up to 31 December 2017. Retrieved data were analyzsd, and bibliometric indicators and maps were presented. KEY FINDINGS: In total, 16 133 documents were retrieved. Most frequently encountered author keywords, other than adherence/compliance, were HIV, hypertension, diabetes mellitus, schizophrenia, depression, osteoporosis, asthma and quality of life. The number of documents published from 2008 to 2017 represented 62.0% (n = 10 005) of the total retrieved documents. The h-index of the retrieved documents was 223. The USA ranked first (43.1%; n = 6959), followed by the UK (8.6%; n = 1384) and Canada (4.5%; n = 796). The USA dominated the lists of active authors and institutions. Top active journals in publishing research on medication adherence were mainly in the field of AIDS. Top-cited articles in the field focused on adherence to anti-HIV medications, the impact of depression on medication adherence and barriers to adherence. CONCLUSION: Adherence among HIV patients dominated the field of medication adherence. Research on medication adherence needs to be strengthened in all countries and in different types of chronic diseases. Research collaboration should also be encouraged to increase research activity on medication adherence in developing countries.

Evaluation of antihypertensive therapy in diabetic hypertensive patients: impact of ischemic heart disease.

UNLABELLED: Macrovascular complications are common in diabetic hypertensive patients. Appropriate antihypertensive therapy and tight blood pressure control are believed to prevent or delay such complication. OBJECTIVE: To evaluate utilization patterns of antihypertensive agents and blood pressure (BP) control among diabetic hypertensive patients with and without ischemic heart disease (IHD). METHODS: Retrospective cohort study of all diabetic hypertensive patients attending Al-watani medical center from August 2006 until August 2007. Proportions of use of different antihypertensive drug classes were compared for all patients receiving 1, 2, 3, or 4 or more drugs, and separately among patients with and without IHD. Blood pressure control (equal or lower 130/80 mmHg) was compared for patients receiving no therapy, monotherapy, or combination therapy and separately among patients with and without IHD. RESULTS: 255 patients were included in the study; their mean age was 64.4 (SD=11.4) years. Sixty one (23.9%) of the included patients was on target BP. Over 60% of the total patients were receiving angiotensin-converting enzyme inhibitors (ACEI)/ angiotensin receptor blocker (ARB), followed by diuretics (40.8%), calcium channel blockers (25.1%) and beta-blockers (12.5%). The majority (> 55%) of patients were either on mono or no drug therapy. More than 55% of patients with controlled BP were using ACE-I. More than half (50.8%) of the patients with controlled BP were on combination therapy while 42.3% of patients with uncontrolled BP were on combination therapy (p=0.24). More patient in the IHD achieved target BP than those in non-IHD group (p=0.019). Comparison between IHD and non-IHD groups indicated no significant difference in the utilization of any drug class with ACE-I being the most commonly utilized in both groups. CONCLUSIONS: Patterns of antihypertensive therapy were generally but not adequately consistent with international guidelines. Areas of improvement include increasing ACE-I drug combinations, decreasing the number of untreated patients, and increasing the proportion of patients with controlled BP in this population.

Prevalence of reduced renal function among diabetic hypertensive patients.

Patients with diabetes mellitus and hypertension are at high risk of vascular complications, particularly, renal deterioration. This study aimed to evaluate the prevalence and the risk factors of reduced renal function corresponding to chronic kidney disease (CKD) stages 3 - 5 among diabetic hypertensive patients. This is a retrospective cohort study of diabetic hypertensive patients attending A-Watani governmental medical center from August 2006 until August 2007. Creatinine clearance (CrCl) was estimated using the Cockcroft-Gault equation. Those with CrCl< 60 ml/ min, corresponding to CDK stages 3 - 5, were considered to have reduced renal function. The prevalence of reduced renal function was calculated, and the risk factors associated with it were evaluated using multiple logistic regression. The following were the results found in this study: (a) the prevalence of reduced renal function among the study patients was 35.5% distributed as follows: (63.5%) had stage 3 CKD, 21.7% had stage 4 and 13% had stage 5 CKD. (b) Patients with reduced renal function were elderly, had a higher number of chronic diseases and had a longer duration of diabetes and hypertension than those with CrCl≥ 60ml/ min. (c) Men had a higher prevalence of reduced renal function than women. (d) Significant predictors of reduced renal function were older age, duration of diabetes and the number of chronic diseases based on logistic regression analysis. Early and continuous screening of renal function among diabetic hypertensive patients is required to implement preventable strategies of end stage renal disease (ESRD). Better control of blood pressure and diabetes mellitus are important.