Mohanad Naji Sahib

Rehydrated sterically stabilized phospholipid nanomicelles of budesonide for nebulization: physicochemical characterization and in vitro, in vivo evaluations

Background Inhaled corticosteroids provide unique systems for local treatment of asthma or chronic obstructive pulmonary disease. However, the use of poorly soluble drugs for nebulization has been inadequate, and many patients rely on large doses to achieve optimal control of their disease. Theoretically, nanotechnology with a sustained-release formulation may provide a favorable therapeutic index. The aim of this study was to determine the feasibility of using sterically stabilized phospholipid nanomicelles of budesonide for pulmonary delivery via nebulization. Methods PEG5000-DSPE polymeric micelles containing budesonide (BUD-SSMs) were prepared by the coprecipitation and reconstitution method, and the physicochemical and pharmacodynamic characteristics of BUD-SSMs were investigated. Results The optimal concentration of solubilized budesonide at 5 mM PEG5000-DSPE was 605.71 ± 6.38 μg/mL, with a single-sized peak population determined by photon correlation spectroscopy and a particle size distribution of 21.51 ± 1.5 nm. The zeta potential of BUD-SSMs was −28.43 ± 1.98 mV. The percent entrapment efficiency, percent yield, and percent drug loading of the lyophilized formulations were 100.13% ± 1.09%, 97.98% ± 1.95%, and 2.01% ± 0.02%, respectively. Budesonide was found to be amorphous by differential scanning calorimetry, and had no chemical interaction with PEGylated polymer according to Fourier transform infrared spectroscopy. Transmission electron microscopic images of BUD-SSMs revealed spherical nanoparticles. BUD-SSMs exhibited prolonged dissolution behavior compared with Pulmicort Respules® (P < 0.05). Aerodynamic characteristics indicated significantly higher deposition in the lungs compared with Pulmicort Respules®. The mass median aerodynamic, geometric standard deviation, percent emitted dose, and the fine particle fraction were 2.83 ± 0.08 μm, 2.33 ± 0.04 μm, 59.13% ± 0.19%, and 52.31% ± 0.25%, respectively. Intratracheal administration of BUD-SSMs 23 hours before challenge (1 mg/kg) in an asthmatic/chronic obstructive pulmonary disease rat model led to a significant reduction in inflammatory cell counts (76.94 ± 5.11) in bronchoalveolar lavage fluid compared with administration of Pulmicort Respules® (25.06 ± 6.91). Conclusion The BUD-SSMs system might be advantageous for asthma or chronic obstructive pulmonary disease and other inflammatory airway diseases.

Solubilization of beclomethasone dipropionate in sterically stabilized phospholipid nanomicelles (SSMs): physicochemical and in vitro evaluations

Background The local treatment of lung disorders such as asthma and chronic obstructive pulmonary disease via pulmonary drug delivery offers many advantages over oral or intravenous routes of administration. This is because direct deposition of a drug at the diseased site increases local drug concentrations, which improves the pulmonary receptor occupancy and reduces the overall dose required, therefore reducing the side effects that result from high drug doses. From a clinical point of view, although jet nebulizers have been used for aerosol delivery of water-soluble compounds and micronized suspensions, their use with hydrophobic drugs has been inadequate. Aim: To evaluate the feasibility of sterically stabilized phospholipid nanomicelles (SSMs) loaded with beclomethasone dipropionate (BDP) as a carrier for pulmonary delivery. Methods 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 5000) polymeric micelles containing BDP (BDP-SSMs) were prepared by the coprecipitation and reconstitution method, and the physicochemical and in vitro characteristics of BDP-SSMs were investigated. Results BDP-SSMs were successfully prepared with a content uniformity and reproducibility suitable for pulmonary administration. The maximum solubility of BDP in SSMs was approximately 1300 times its actual solubility. The particle size and zeta potential of BDP-SSMs were 19.89 ± 0.67 nm and −28.03 ± 2.05 mV, respectively. The SSMs system slowed down the release of BDP and all of the aerodynamic values of the aerosolized rehydrated BDP-SSMs were not only acceptable but indicated a significant level of deposition in the lungs. Conclusion The SSM system might be an effective way of improving the therapeutic index of nebulized, poorly soluble corticosteroids.

Physician adherence to hypertension treatment guidelines and drug acquisition costs of antihypertensive drugs at the cardiac clinic: a pilot study.

Prescribing pattern surveys are one of the pharmacoepidemiological techniques that provide an unbiased picture of prescribing habits. Prescription surveys permit the identification of suboptimal prescribing patterns for further evaluation. The aims of this study were to determine the prescribing trend, adherence of the prescribers to the guideline, and the impact of drug expenditure on drug utilization at the cardiac clinic of Penang Hospital, Malaysia. This was a cross-sectional study. Demographic data of the patients, diagnoses and the drugs prescribed were recorded. The average drug acquisition costs (ADAC) were calculated for each antihypertensive drug class on a daily and annual basis. Adherence to the guideline was calculated as a percentage of the total number of patients. A total of 313 individuals fulfilled the inclusion criteria. The average age of the study population was 59.30 ± 10.35 years. The mean number of drugs per prescription in the study was 2.09 ± 0.78. There were no significant differences in the demographic data. Antihypertensive drugs were used in monotherapy and polytherapy in 20.8% and 79.2% of the patients, respectively. Adherence to the guideline regarding prescription occurred in 85.30% of the patients. The lowest priced drug class was diuretics and the highest was angiotensin-receptor blockers. In conclusion, the total adherence to the guideline was good; the adherence percentage only slightly decreased with a co-existing comorbidity (such as diabetes mellitus). The use of thiazide diuretics was encouraged because they are well tolerated and inexpensive, and perindopril was still prescribed for diabetic patients since it is relatively cheap (generic drug) and its daily dosage is beneficial.

Incorporation of Beclomethasone Dipropionate into Polyethylene Glycol‐Diacyl Lipid Micelles as a Pulmonary Delivery System

Strategy, Management and Health Policy Enabling Technology, Genomics, Proteomics Preclinical Research Preclinical Development Toxicology, Formulation Drug Delivery, Pharmacokinetics Clinical Development Phases I‐III Regulatory, Quality, Manufacturing Postmarketing Phase IV

AERODYNAMIC CHARACTERIZATION OF BECLOMETHASONE DIPROPIONATE FROM BECLATE-50 INHALER® BY HPLC-UV

A simple yet sensitive high performance liquid chromatography (HPLC) method was developed and validated for the determination of aerodynamic characteristics of the emitted dose of beclomethasone dipropionate from Beclate-50 Inhaler®. The mobile phase consisted of a mixture of acetonitrile and 10 mM ammonium acetate (70:30% v/v) adjusted to pH 5 with orthophosphoric acid. The HPLC analysis was run at a flow rate of 1 mL/min using a C18 column at a UV detection wavelength of 254 nm. The method was validated for specificity, linearity, precision, accuracy, limit of quantification, limit of detection, robustness, and solution stability. The calibration curve was linear over a concentration range of 0.03–62.50 µg/mL (r2 = 0.9999) with limit of detection and limit of quantification of 0.01 and 0.03 µg/mL, respectively. The intra-day and inter-day precision and accuracy were between 0.02 and 1.89% and −1.08 and 2.62%, respectively. The method was successfully applied to the aerodynamic characterization of both the fine particle and the emitted doses of beclomethasone dipropionate from Beclate-50 Inhaler®.

Psychometric properties of the Malay version of the Osteoporosis Health Belief Scale (OHBS-M) among Type 2 diabetic patients

The aims of this study were to translate and examine the psychometric properties of the Malaysian version of the Osteoporosis Health Belief Scale (OHBS‐M) among type 2 diabetes patients (T2DM) and to assess the correlation between osteoporosis knowledge, health belief and self‐efficacy scales, as well as assess the osteoporosis risk in the sample population using quantitative ultrasound measurement (QUS).

Is there a link between osteoporosis and type 1 diabetes? Findings from a systematic review of the literature

IntroductionDiabetes mellitus (DM) is a pandemic and heterogeneous metabolic disorder with significant morbidity and mortality. In addition, osteoporosis (OP) is a silent disease that constitutes an enormous socioeconomic crisis, with a harmful impact on morbidity and mortality. Therefore, this systematic review focuses on the association between OP and type 1 diabetes mellitus (T1DM).MethodsSystematic reviews of full-length articles published in English from January 1950 to October 2010 were identified in PubMed and other available electronic databases at Universiti Sains Malaysia Library Database. The following keywords were used for the search: T1DM, insulin, OP, bone mass, and skeletal. Studies of more than 20 patients with T1DM were included.ResultsFifty studies were identified. In general, most of the studies showed unambiguous evidence for a decrease in bone mineral density in T1DM.ConclusionsScreening, identification and prevention of potential risk factors for OP in T1DM patients are crucial and important in terms of preserving a good quality of life in diabetic patients. Patient education about an adequate calcium and vitamin D intake and regular exercise are important for improving muscle strength and balance, and specific measures for preventing falls. Furthermore, adequate glycemic control and the prevention of diabetic complications are the starting point of therapy in T1DM.

The Prevalence of Osteopenia and Osteoporosis Among Malaysian Type 2 Diabetic Patients Using Quantitative Ultrasound Densitometer

Background: Type 2 Diabetes Mellitus (T2DM) and osteoporosis are both chronic conditions and the relationship between them is complex. Objective: The aims of this study were to assess the prevalence of Low Bone Mineral density (LBMD, i.e., osteopenia and osteoporosis), as well as, the difference and associations between Quantitative Ultrasound Scan (QUS) parameters with socio-demographic data and clinical related data among T2DM in Penang, Malaysia. Method: An observational, cross-sectional study with a convenient sample of 450 T2DM patients were recruited from the outpatient diabetes clinic at Hospital Pulau Pinang (HPP) to measure Bone Mineral Density (BMD) at the heel bone using QUS. In addition, a self-reported structured questionnaire about the socio-demographic data and osteoporosis risk factors were collected. Moreover, the study included the retrospective collection of clinical data from patients’ medical records. Results: The mean value of T-score for normal BMD, osteopenic and osteoporotic patients’ were (-0.41±0.44), (-1.65±0.39) and (-2.76±0.27), respectively. According to QUS measurements, more than three quarters of T2DM patients (82%) were at high risk of abnormal BMD. The results showed that QUS scores were significantly associated with age, gender, menopausal duration, educational level and diabetic related data. Moreover, the QUS parameters and T-scores demonstrated significant negative correlation with age, menopausal duration, diabetic duration and glycaemic control, as well as, a positive correlation with body mass index and waist to hip ratio. The current study revealed that none of the cardiovascular disease risk factors appear to influence the prevalence of low BMD among T2DM Malaysian patients. Conclusion: The study findings revealed that the assessment of T2DM patients’ bone health and related factor are essential and future educational programs are crucial to improve osteoporosis management.

Psychometric properties and assessment of the Osteoporosis Health Belief Scale among the general Arabic population

Background Any educational program should be implemented with a good understanding of the population’s beliefs. Therefore, the aims of this study were to validate the Arabic version of the Osteoporosis Health Belief Scale (OHBS-A) and assess the osteoprotective attitude among the Iraqi population. Methods A cross-sectional design, with a random cluster sampling method from the community, was used. The forward–backward–forward translation method was used to translate the questionnaire from English to Arabic. In addition, the Arabic version of Osteoporosis Knowledge Tool (OKT-A) and the Arabic version of Osteoporosis Self-Efficacy Scale (OSES-A) were used to assess the osteoprotective behaviors. Results The results showed good face validity and reliability. The construct validity analysis showed seven factors that explain 72.82% of the variance. In addition, the results revealed a low health belief score (149.95±35.936) with only 36.67% of the study population found to have a high OHBS-A level. The results showed significant differences among employment status, marital status, and osteoporosis (OP) awareness groups in relation to total OHBS-A scores. In addition, there were significant associations between age groups and OP awareness with health belief levels. Moreover, both exercise and calcium intake subscales of the Osteoporosis Knowledge Tool (OKT) positively correlated with all OHBS-A subscales. Exercise and calcium intake subscales of Osteoporosis Self-Efficacy Scale (OSES) positively correlated with the perceived susceptibility and perceived barriers toward exercise and calcium intake. The binary logistic regression analysis showed that OKT levels, OSES levels, and age were predictors of OHBS-A levels. Conclusion Besides cultural obstacles, an educational program for both genders and all age groups is important and should be tailored according to culture needs.