Mutasim Al-Ghazawi

Comprehensive assessment of treatment related problems in hospitalized medicine patients in Jordan.

Objectives The aim of this study was to identify the prevalence and characteristics of treatment related problems (TRPs) in hospitalized internal medicine patients in Jordan as well as to identify diseases and drugs associated with each specific TRP. We have also aimed at investigating physicians’ acceptance of recommendations made by clinical pharmacist and to identify the outcomes of pharmacist interventions. Setting Internal medicine department of a general hospital in Jordan. Methods We have utilized a systematic, prospective, bedside, comprehensive clinical assessment approach that allowed us to effectively identify, communicate and follow up TRPs. Main outcome measures: prevalence and nature of identified TRPs, clinical significance of TRPs, associated diseases and drugs and clinical outcomes of clinical pharmacist interventions. Results 402 patients were included in the study. The average number of the identified TRPs was 9.35. Fifty-three percent of identified TRPs were classified as major and 28% were classified as moderate. Ninety-one percent of the recommendations were accepted by physicians. Efficacy related problems were the most common TRP category followed by safety related problems and indication related problems. Sixty-four percent of the TRPs were resolved or prevented through the clinical pharmacist intervention. Conclusions We have found that prevalence of TRPs is substantially high among patients hospitalized at the internal medicine department. TRPs related to Dosage regimens, untreated conditions, patient monitoring, drug interactions, and drug choices were the most common. Most of TRPs identified by pharmacists were clinically significant. Pharmacists’ interventions contributed substantially to the resolving of many of the identified TRPs. Patients suffering from higher number of medical conditions and receiving higher number of medications should be given the priority for clinical pharmacy service in hospitalized internal medicine patients.

Sustained Release Characteristics of Tablets Prepared with Mixed Matrix of Sodium Carrageenan and Chitosan: Effect of Polymer Weight Ratio, Dissolution Medium, and Drug Type

The interpolymeric complexation of carrageenan and chitosan was investigated for its effect on drug release from polymeric matrices in comparison to single polymers. For this purpose, matrices with carrageenan: chitosan (CG:CS) ratios of 100%, 75%, 50%, 25%, and 0% were prepared at 1:1 drug to polymer ratio. The effect of dissolution medium and drug type on drug release from the formulations was addressed. Two model drugs were utilized: diltiazem HCl (DZ) as a salt of a basic drug and diclofenac Na (DS) as a salt of an acidic drug. Three dissolution media were used: water, simulated gastric fluid (SGF), and simulated intestinal fluid (SIF). Some combinations of the two polymers showed remarkable sustained release effect on DZ in comparison to the single polymers in water and SGF. However, no apparent effect for the combination on DZ release was shown in SIF. The medium effect was explained by the necessity of chitosan ionization, which could be attained by the acidic SGF or microacidic environment created by the used acidic salt of DZ in water, but not in SIF. An interaction between the medium type and CG:CS ratio was also found. With DS, the polymer combinations had similar dissolution profiles to those of the single polymers in water and SIF, which was explained by the lack of chitosan ionization by the medium or the drug basic salt. The dissolution profiles could not be obtained in SGF, which was attributed to the conversion of DS into diclofenac free acid. The importance of chitosan ionization for its interaction with CG to have an effect on the release of DS was demonstrated by performing dissolution of SGF presoaked tablets of DS in SIF, which showed an effect of combining the two polymers on sustaining the drug release.

Development of a biphasic dissolution test for Deferasirox dispersible tablets and its application in establishing an in vitro–in vivo correlation

In a biphasic dissolution medium, the integration of the in vitro dissolution of a drug in an aqueous phase and its subsequent partitioning into an organic phase is hypothesized to simulate the in vivo drug absorption. Such a methodology is expected to improve the probability of achieving a successful in vitro-in vivo correlation. Dissolution of Dispersible tablets of Deferasirox, a biopharmaceutics classification system type II compound, was studied in a biphasic dissolution medium using a flow-through dissolution apparatus coupled to a paddle apparatus. The experimental parameters associated with dissolution were optimized to discriminate between Deferasirox dispersible tablets of different formulations. The dissolution profiles obtained from this system were subsequently used to construct a level A in vitro-in vivo correlation.

Development of quantitative structure-property relationship models for pseudoternary microemulsions formulated with nonionic surfactants and cosurfactants: application of data mining and molecular modeling.

Data mining, computer-aided molecular modeling, descriptor calculation and multiple linear regression techniques were utilized to produce statistically significant and predictive models for O/W and W/O microemulsions. The literature was scanned over the last 20 years, subsequently, 68 phase diagrams from eight different references were collected. Molecular modeling techniques were then applied on the components of the microemulsion systems to generate plausible 3-D structures. Subsequently, various physicochemical descriptors were calculated based on the resulting 3-D structures. The generated descriptors were correlated with microemulsion existence areas utilizing multiple linear regression analysis (MLR). The generated models were statistically cross-validated and were found to be of significant predictive power. Furthermore, the resulting models allowed better understanding of the process of microemulsion formation.

Influence of ethanol on swelling and release behaviors of Carbopol®-based tablets

The aim of this work was to investigate the effect of ethanol on the in vitro swelling and release behaviors of Carbopol®-based tablets. The swelling behavior of drug-free compacts and the release of model drugs (metformin HCl, caffeine and theophylline) from matrix tablets were evaluated in acidic and buffered media with 0, 20 and 40% (v/v) ethanol. Release data were analyzed by fitting to Higuchi and Peppas models and calculation of similarity factor (f2). ANOVA tests were performed to determine significant factors on swelling and release. It was found that ethanol affects swelling and erosion of drug-free Carbopol® compacts, and the effect was highly dependent on medium pH. For matrix tablets, no dose dumping due to ethanol was manifested. The release rate and mechanism, however, were significantly affected by ethanol concentration as indicated by ANOVA applied to the constant, KH, from Higuchi model and the exponent, n, from Peppas model, respectively. The effect of ethanol on release was further confirmed by similarity factor results, which indicated that ethanol led to different release profiles (f2 < 50) in seven of eight cases for matrices containing metformin HCl and in three of eight cases for matrices containing caffeine and theophylline.

Development of a predictive in vitro dissolution for clarithromycin granular suspension based on in vitro-in vivo correlations

The objective of this study was to evaluate the in vitro behavior of different clarithromycin granular suspensions based on a developed in vitro-in vivo correlation model, using one reference and two test formulations. In vitro release rate data were obtained for each product using the USP apparatus II, operated at 50 rpm under different pH conditions. The dissolution efficiency was used to analyze the dissolution data. In vivo study was performed on six healthy male volunteers under fasting condition. Correlation was made between in vitro release and in vivo absorption. A linear model was developed using percent absorbed data versus percent dissolved data from the three products. Dissolution condition of 0.1N HCl for 1 h and then phosphate buffer at pH 6.8 was found to be the most discriminating dissolution method. Rate of absorption for the reference as estimated by Wagner-Nelson deconvolution was correlated with in vitro release with a correlation coefficient of 0.99. The in vivo results for the two test products were compared to the predicted values using the reference model with a correlation coefficient of 0.94. Furthermore, multiple level C correlations were obtained for some pharmacokinetic parameters with the corresponding in vitro kinetic parameters with correlation coefficients exceeding 0.90. Moreover, the interpretation of the in vitro and in vivo data with reference to formulations was discussed.

Wound infiltration with bupivacaine 0.5% with or without adrenaline does not decrease pain after thyroidectomy. A randomized controlled study

Objectives: To study the effect of local wound infiltration with and without adrenaline on pain perception after thyroidectomy using the visual analog score (VAS). Methods: A prospective randomized controlled double-blinded study was conducted between May 2015 and June 2016 at The University of Jordan Hospital, Amman, Jordan. Eighty-nine patients undergoing planned thyroidectomy were included in the study. Patients were divided randomly into 3 groups: Group A, local wound infiltration with bupivacaine 0.5% was administered; Group B, bupivacaine 0.5% with adrenaline was administered; Group C (control), no infiltration was performed. Standardized thyroidectomies were performed in the 3 groups. Pain perception was measured using VAS at 2, 4, 6, 12, and 24 hours after surgery. A comparison between the 3 groups was carried out. Results: No significant differences among the 3 groups were observed at all time points (p=0.246). Visual analog scores were significantly lower at 12 and 24 hours after operations. Conclusion: Local wound infiltration with bupivacaine 0.5% does not decrease pain perception after thyroidectomy performed under general anesthesia, and adding adrenaline does not enhance its effect.