Prevalence and Factors that Influence Potentially Inappropriate Medication Use among Thai Elderly in Primary Care Settings

Background Older age increases the likelihood of chronic diseases and polypharmacy with the likelihood of potentially inappropriate medications (PIMs) in secondary and tertiary care levels, but in the primary care settings of Thailand there still is a need for more evidence. This study aimed to examine the prevalence of PIM in primary care settings, and to identify factors that influence the use of PIM. Methods A cross-sectional retrospective study was conducted in 2017. Eight primary care units from four regions of Thailand were randomly selected. People aged ≥ 60 years in the eight units were studied as participants. The List of Risk Drugs for Thai Elderly (LRDTE) was used as the reference. Multivariate logistic regression was carried out to identify factors that influence. Results A total of 4,848 patients aged ≥60 years with 20,671 prescriptions were studied. The mean age was 70.7±8.3 years for males, and 61.2% for females. A little more than 5% (5.1%) had ≥ 3 chronic diseases and 15.0% received polypharmacy ( ≥5 medications). The prevalence of prescriptions with PIMs was 65.9%. The most frequent PIMs were antidepressants: amitriptyline (28.1%), antihistamines: dimenhydrinate (22.4%) and chlorpheniramine maleate (CPM) (11.2%); and Benzodiazepines: lorazepam (6.5%). Three factors that significantly influenced prescribing of PIMs were polypharmacy (adjusted OR 3.51; 95% CI 2.81-4.32), having ≥3 chronic diseases (adjusted OR 1.44; 95% CI 1.04-2.01), and age ≥75 years (adjusted OR 1.18; 95% CI 1.01-1.38). Conclusion More than two-thirds of elderly Thai patients in the primary care settings were prescribed PIMs. Multidisciplinary prescription review and PIM screening in patients aged ≥75 years who have ≥3 chronic diseases or polypharmacy should be implemented in primary care and supportive computerized PIMs alert system is needed.

The Preferred Premedication Order to Prevent Infusion Reactions in Patients with Breast Cancer Receiving Pertuzumab Plus Trastuzumab and Docetaxel

Aims:Pertuzumab plus trastuzumab and docetaxel is a standard regimen for human epidermal growth factor receptor 2 (HER2)-positive breast cancer in the metastatic, adjuvant, and neoadjuvant settings. Infusion reaction represents one of the common side effects of anti-HER2 agents. There is no standard premedication to prevent infusion reactions, although antihistamines, acetaminophen, and/or corticosteroids are often used for this purpose. This study evaluated the ability of premedication to prevent induction reactions in patients receiving pertuzumab, trastuzumab, and docetaxel. Methods: This retrospective, single-institute study assessed infusion reactions in 72 women with HER2-positive early breast cancer who received pertuzumab, trastuzumab, and docetaxel between November 2018 and April 2021. Thirty-six patients received premedication consisting of oral acetaminophen prior to pertuzumab and trastuzumab administration and dexamethasone and D-chlorpheniramine maleate intravenously prior to docetaxel administration (previous regimen). Thirty-six patients received premedication consisting of acetaminophen, dexamethasone, and D-chlorpheniramine maleate sequentially prior to pertuzumab, trastuzumab, and docetaxel administration (current regimen). Results: The rates of infusion reaction after the initial injection were 55.6 and 16.7% in the previous and current regiment groups, respectively (p = 0.001). Trastuzumab more frequently caused infusion reactions than pertuzumab and docetaxel. Chills, vomiting, and nausea were the major symptoms of infusion reactions. Conclusion: Premedication featuring the upfront use of dexamethasone and D-chlorpheniramine maleate prior to the administration of anti-HER2 targeted agents significantly prevented infusion reactions.

Concentration Dependent Single Chain Properties of Poly(Sodium 4-Styrenesulfonate) Subjected to Aromatic Interactions with Chlorpheniramine Maleate Studied by Diafiltration and Synchrotron-SAXS

The polyelectrolyte poly(sodium 4-styrenesulfonate) undergoes aromatic–aromatic interaction with the drug chlorpheniramine, which acts as an aromatic counterion. In this work, we show that an increase in the concentration in the dilute and semidilute regimes of a complex polyelectrolyte/drug 2:1 produces the increasing confinement of the drug in hydrophobic domains, with implications in single chain thermodynamic behavior. Diafiltration analysis at polymer concentrations between 0.5 and 2.5 mM show an increase in the fraction of the aromatic counterion irreversibly bound to the polyelectrolyte, as well as a decrease in the electrostatic reversible interaction forces with the remaining fraction of drug molecules as the total concentration of the system increases. Synchrotron-SAXS results performed in the semidilute regimes show a fractal chain conformation pattern with a fractal dimension of 1.7, similar to uncharged polymers. Interestingly, static and fractal correlation lengths increase with increasing complex concentration, due to the increase in the amount of the confined drug. Nanoprecipitates are found in the range of 30–40 mM, and macroprecipitates are found at a higher system concentration. A model of molecular complexation between the two species is proposed as the total concentration increases, which involves ion pair formation and aggregation, producing increasingly confined aromatic counterions in hydrophobic domains, as well as a decreasing number of charged polymer segments at the hydrophobic/hydrophilic interphase. All of these features are of pivotal importance to the general knowledge of polyelectrolytes, with implications both in fundamental knowledge and potential technological applications considering aromatic-aromatic binding between aromatic polyelectrolytes and aromatic counterions, such as in the production of pharmaceutical formulations.

Utilising Co-Axial Electrospinning as a Taste-Masking Technology for Paediatric Drug Delivery

The present study describes the use of two taste-masking polymers to fabricate a formulation of chlorpheniramine maleate for paediatric administration. Co-axial electrospinning was utilized to create layered nanofibres; the two polymers, Eudragit® E PO and Kollicoat® Smartseal, were alternated between the core and the shell of the system in order to identify the optimum taste-masked formulation. The drug was loaded in the core on all occasions. It was found that the formulation with Kollicoat® Smartseal in the core with the drug, and Eudragit® E PO in the shell showed the most effective taste-masking compared to the other formulations. These fibres were in the nano-range and had smooth morphology as verified by scanning electron microscopy. Solid-state characterization and thermal analysis confirmed that amorphous solid dispersions were formed upon electrospinning. The Insent E-tongue was used to assess the taste-masking efficiency of the samples, and it was found that this formulation was undetectable by the bitter sensor, indicating successful taste-masking compared to the raw version of the drug. The E-tongue also confirmed the drug’s bitterness threshold as compared to quinine HCl dihydrate, a parameter that is useful for formulation design and taste-masking planning.

Implementation of different separation techniques for resolving ternary mixture of Paracetamol, Pseudoephedrine Hydrochloride and Chlorpheniramine maleate with further quantification

Due to the wide applicability of separation techniques that rely on the property of differential migration in pharmaceutical formulations analysis, different analytical strategies have been proposed to resolve mixtures of multi-components pharmaceuticals. Three separation methods were developed and validated for the simultaneous determination of Paracetamol (PAR), Pseudoephedrine HCl (PSE) and Chlorpheniramine maleate (CHP). The first method is a thin-layer chromatographic (TLC) separation, followed by densitometric measurement. The separation was carried out on aluminium sheet of silica gel 60 F254 using ethanol:chloroform:ammonia (1:7:0.4, by volume) as the mobile phase. Determination of PAR, PSE and CHP was successfully applied over the concentration ranges of 3–25 µg/band, 0.5–10 µg/band and 0.1–6 µg/band, respectively. The second method is HPLC separation that was achieved on C18 column using the mobile phase acetonitrile:phosphate buffer pH 5 (10:90, v/v) at a flow rate 1 mL min−1. PAR, PSE and CHP were determined by HPLC in concentration ranges of 5–400 μg mL−1, 2–40 μg mL−1 and 0.5–16 μg mL−1, respectively. The third method is a capillary electrophoresis (CE) separation. The electrophoretic separation was achieved using 20 mM phosphate buffer (pH 6.5) at 20 kV. The linearity was reached over concentration ranges of 30–250 μg mL−1, 5–50 μg mL−1 and 0.8–20 μg mL−1 for PAR, PSE and CHP, respectively. The developed methods were validated with respect to linearity, precision, accuracy and system suitability. The proposed methods were successfully applied for bulk powder and dosage form analysis with RSD of precision <2%. Moreover, statistical comparison with the official methods confirms the methods' validity.