Preparation and Characterization of Theophylline Controlled Release Matrix System Incorporating Poloxamer 407, Stearyl Alcohol, and Hydroxypropyl Methylcellulose: A Novel Formulation and Development Study.

BACKGROUND: Theophylline (THN), a bronchodilator with potential applications in emerging conditions like COVID-19, requires a controlled-release delivery system due to its narrow therapeutic range and short half-life. This need is particularly crucial as some existing formulations demonstrate impaired functionality. This study aims to develop a new 12-h controlled-release matrix system (CRMS) in the form of a capsule to optimize dosing intervals. METHODS: CRMSs were developed using varying proportions of poloxamer 407 (P-407), stearyl alcohol (STA), and hydroxypropyl methylcellulose (HPMC) through the fusion technique. Their in vitro dissolution profiles were then compared with an FDA-approved THN drug across different pH media. The candidate formulation underwent characterization using X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and thermogravimetric analysis. Additionally, a comprehensive stability study was conducted. RESULTS: In vitro studies showed that adjusting the concentrations of excipients effectively controlled drug release. Notably, the CRMS formulation 15 (CRMS-F15), which was composed of 30% P-407, 30% STA, and 10% HPMC, closely matched the 12 h controlled-release profile of an FDA-approved drug across various pH media. Characterization techniques verified the successful dispersion of the drug within the matrix. Furthermore, CRMS-F15 maintained a consistent controlled drug release and demonstrated stability under a range of storage conditions. CONCLUSIONS: The newly developed CRMS-F15 achieved a 12 h controlled release, comparable to its FDA-approved counterpart.

Effect of Hydration Forms and Polymer Grades on Theophylline Controlled-Release Tablet: An Assessment and Evaluation.

BACKGROUND: Drug release from controlled release delivery systems is influenced by various factors, including the polymer's grade and the drug's hydration form. This study aimed to investigate the impact of these factors on the controlled release of theophylline (THN). This research compares the monohydrate form found in branded products with the anhydrous form in generic equivalents, each formulated with different polymer grades. METHODS: Quality control assessment was conducted alongside in vitro evaluation, complemented by various analytical techniques such as X-ray diffraction (XRD) and scanning electron microscopy (SEM). Additionally, thermal analyses using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were employed. RESULTS: Quality control assessments demonstrated that the generic tablets exhibited lower average weight and resistance force compared to the branded ones. In vitro tests revealed that generic tablets released contents within 120 min, compared to 720 min for the branded counterpart. Characterization using XRD and SEM identified disparities in crystallinity and particle distribution between the three samples. Additionally, the thermal analysis indicated consistent endothermic peaks across all samples, albeit with minor variations in heat flow and decomposition temperatures between the two products. CONCLUSIONS: This study demonstrated that variations in polymer grade and hydration form significantly impact THN release.

Nanomedicines: Emerging Platforms in Smart Chemotherapy Treatment-A Recent Review.

Cancer continues to pose one of the most critical challenges in global healthcare. Despite the wide array of existing cancer drugs, the primary obstacle remains in selectively targeting and eliminating cancer cells while minimizing damage to healthy ones, thereby reducing treatment side effects. The revolutionary approach of utilizing nanomaterials for delivering cancer therapeutic agents has significantly enhanced the efficacy and safety of chemotherapeutic drugs. This crucial shift is attributed to the unique properties of nanomaterials, enabling nanocarriers to transport therapeutic agents to tumor sites in both passive and active modes, while minimizing drug elimination from delivery systems. Furthermore, these nanocarriers can be designed to respond to internal or external stimuli, thus facilitating controlled drug release. However, the production of nanomedications for cancer therapy encounters various challenges that can impede progress in this field. This review aims to provide a comprehensive overview of the current state of nanomedication in cancer treatment. It explores a variety of nanomaterials, focusing on their unique properties that are crucial for overcoming the limitations of conventional chemotherapy. Additionally, the review delves into the properties and functionalities of nanocarriers, highlighting their significant impact on the evolution of nanomedicine. It also critically assesses recent advancements in drug delivery systems, covering a range of innovative delivery methodologies. Finally, the review succinctly addresses the challenges encountered in developing nanomedications, offering insightful perspectives to guide future research in this field.

Novel insights into the anti-asthmatic effect of Raphanus sativus L. (Raphani Semen): Targeting immune cells, inflammatory pathways and oxidative stress markers.

ETHNOPHARMACOLOGICAL RELEVANCE: Raphanus sativus L. is a well-known medicinal plant with traditional therapeutic applications in various common ailments including inflammation and asthma. AIMS OF THE STUDY: This study aimed to evaluate the chemical composition and anti-asthmatic potential of the hydro-methanolic extract of the leaves of R. sativus L. (Rs.Cr) using various in vitro and in vivo investigations. MATERIALS AND METHODS: The Rs.Cr was subjected to preliminary phytochemical analysis and HPLC profiling. The safety was assessed through oral acute toxicity tests in mice. The antiasthmatic effect of the extract was studied using milk-induced leukocytosis and ovalbumin (OVA)-induced allergic asthma models established in mice. While mast cell degranulation and passive paw anaphylaxis models were established in rats. Moreover, effect of the extract was studied on various oxidative and inflammatory makers. The antioxidant effect of the extract was also studied by in vitro DPPH method. RESULTS: The HPLC profiling of Rs.Cr showed the presence of important polyphenols in a considerable quantity. In toxicity evaluation, Rs.Cr showed no sign of morbidity or mortality with LD50 < 2000 mg/kg. The extract revealed significant mast cell disruption in a dose-dependent manner compared to the intoxicated group. Similarly, treatment with Rs.Cr and dexamethasone significantly (p < 0.001) reduced paw edema volume. Subcutaneous injection of milk at a dose of 4 mL/kg, after 24 h of its administration, showed an increase in the leukocyte count in the intoxicated group. Similarly, mice treated with dexamethasone and Rs.Cr respectively showed a significant decrease in leukocytes and eosinophils count in the ovalbumin-induced allergic asthma model. The extract presented a significant (p˂0.001) alleviative effect on the levels of SOD and GSH, MDA, IL-4, IL-5, and IL-13 in a dose-dependent manner as compared to the intoxicated group. Furthermore, the histological evaluation also revealed a notable decrease in inflammatory and goblet cell count with reduced mucus production. CONCLUSION: The current study highlights mechanism-based novel insights into the anti-asthmatic potential of R. sativus that also strongly supports its traditional use in asthma.

An Integrated Computational Approaches for Designing of Potential Piperidine based Inhibitors of Alzheimer Disease by Targeting Cholinesterase and Monoamine Oxidases Isoenzymes.

The study aimed to evaluate the potential of piperidine-based 2H chromen-2-one derivatives against targeted enzymes, i.e., cholinesterase's and monoamine oxidase enzymes. The compounds were divided into three groups, i.e., 4a-m ((3,4-dimethyl-7-((1-methylpiperidin-4-yl)oxy)-2H-chromen-2-one derivatives), 5a-e (3,4-dimethyl-7-((1-methypipridin-3-yl)methoxy)-2H-chromen-2-one derivatives), and 7a-b (7-(3-(3,4-dihydroisoquinolin-2(1H)-yl)propoxy)-3,4-dimethyl-2H-chromen-2-one derivatives) with slight difference in the basic structure. The comprehensive computational investigations were conducted including density functional theories studies (DFTs), 2D-QSAR studies, molecular docking, and molecular dynamics simulations. The QSAR equation revealed that the activity of selected chromen-2-one-based piperidine derivatives is being affected by the six descriptors, i.e., Nitrogens Count, SdssCcount, SssOE-Index, T-2-2-7, ChiV6chain, and SssCH2E-Index. These descriptor values were further used for the preparation of chromen-2-one based piperidine derivatives. Based on this, 83 new derivatives were created from 7 selected parent compounds. The QSAR model predicted their IC50 values, with compound 4 k and 4kk as the most potent multi-targeted derivative. Molecular docking results exhibited these compounds as the best inhibitors; however, 4kk exhibited greater activity than the parent compounds. The results were further validated by molecular dynamic simulation studies along with the suitable physicochemical properties. These results prove to be an essential guide for the further design and development of new piperidine based chromen-2-one derivatives having better activity against neurodegenerative disorder.

UPLC-Q-TOF-MS profiling of Viola stocksii Boiss. and evaluation of aphrodisiac potential and risk factors associated with erectile dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: Viola stocksii Boiss. locally known as makhni or makhanr booti, is an important medicinal food plant with multiple therapeutic applications, including erectile dysfunction (ED). It is mixed with butter and used for boosting energy and sexual health in the subcontinent. AIMS OF THE STUDY: This study was designed to evaluate the chemical composition, aphrodisiac potential and effect of V. stocksii on the risk factors associated with ED. METHODOLOGY: The hydroethanolic extract of V. stocksii (HEEVS) was prepared through the microwave-assisted extraction (MAE) technique. The chemical composition was evaluated using preliminary phytochemical screening and UPLC-Q-TOF-MS analysis. Metals and minerals analysis was performed by an atomic absorption spectrophotometer. The aphrodisiac activity of HEEVS was evaluated using an in vivo aphrodisiac model established in male albino rats and the effect on various sexual parameters such as mount, intromission, ejaculation frequencies and mount, intromission, ejaculation latencies, postejaculatory interval, penile reflexes and serum hormone concentration were analyzed. The effect of HEEVS on various risk factors associated with ED, including prostate cancer (PC), bacterial infections, diabetes and obesity, was evaluated using various in vitro assays. Moreover, four compounds were selected from the UPLC-Q-TOF-MS profile and evaluated for in silico computational analysis against phosphodiesterase-5 (PDE-5) for possible interaction. FINDINGS: The phytochemical screening revealed the presence of various secondary metabolites in HEEVS, while 58 compounds were tentatively identified in the UPLC-Q-TOF-MS analysis. Various important minerals and metals such as zinc, calcium, cadmium and magnesium were detected in the atomic absorption spectrometry analysis. The in vivo aphrodisiac evaluation showed a significant (p < 0.05) increase in the mount, intromission and ejaculation frequencies and a decrease in the mount, intromission latencies and post-ejaculatory intervals at a dose of 300 mg/kg. A marked (p < 0.05) increase was observed in the concentration of serum testosterone and luteinizing hormones in HEEVS treated animals with a significant increase in total penile reflexes. The extract displayed significant anti-prostate cancer activity and a potential antibacterial spectrum against E. coli and S. aureus, with MIC50 values of 215.72 µg/mL and 139.05 µg/mL, respectively. Similarly, HEEVS was found active towards pancreatic lipase (67.34 ± 1.03%), α-glucosidase (3.87 ± 0.54 mmol ACAE/g d.w.) and α-amylase (6.98 ± 1.63 mmol ACAE/g d.w.). The in silico docking study presented a potential interaction between the selected compounds and residues of the active site of PDE-5. CONCLUSION: This report highlights the aphrodisiac potential of V. stocksii and provides experimental support for its traditional use in ED with an attenuative effect on the risk factors associated with ED. Moreover, the chemical composition displayed the presence of functional phytoconstituents and minerals in HEEVS and paves the way for the isolation of compounds with potent aphrodisiac activity.

Evaluation of anticancer potential of tetracene-5,12-dione (A01) and pyrimidine-2,4-dione (A02) via caspase 3 and lactate dehydrogenase cytotoxicity investigations.

Cancer stands as a significant global cause of mortality, predominantly arising from the dysregulation of key enzymes and DNA. One strategic avenue in developing new anticancer agents involves targeting specific proteins within the cancer pathway. Amidst ongoing efforts to enhance the efficacy of anticancer drugs, a range of crucial medications currently interact with DNA at the molecular level, exerting profound biological effects. Our study is driven by the objective to comprehensively explore the potential of two compounds: (7S,9S)-7-[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione (A01) and 5-fluoro-1H-pyrimidine-2,4-dione (A02). These compounds have demonstrated marked efficacy against breast and cervical cancer cell lines, positioning them as promising anticancer candidates. In our investigation, A01 has emerged as a particularly potent candidate, with its potential bolstered by corroborative evidence from lactate dehydrogenase release and caspase-3 activity assays. On the other hand, A02 has exhibited remarkable anticancer potential. To further elucidate their molecular mechanisms and interactions, we employed computational techniques, including molecular docking and molecular dynamics simulations. Notably, our computational analyses suggest that the A01-DNA complex predominantly interacts via the minor groove, imparting significant insights into its mechanism of action. While earlier studies have also highlighted the anticancer activity of A01, our research contributes by providing a deeper understanding of its binding mechanisms through computational investigations. This knowledge holds potential for designing more effective drugs that target cancer-associated proteins. These findings lay a robust groundwork for future inquiries and propose that derivatives of A01 could be synthesized as potent bioactive agents for cancer treatment. By elucidating the distinctive aspects of our study's outcomes, we address the concern of distinguishing our findings from those of prior research.

Repurposing of Strychnine as the Potential Inhibitors of Aldo-keto Reductase Family 1 Members B1 and B10: Computational Modeling and Pharmacokinetic Analysis.

AKR1B1 and AKR1B10 are important members of aldo-keto reductase family which plays a significant role in cancer progression by modulating cellular metabolism. These enzymes are involved in various metabolic processes, including the synthesis and metabolism of hormones, detoxification of reactive aldehydes, and the reduction of various endogenous and exogenous compounds. This study aimed to explore the potential of strychnine as an anticancer agent by targeting AKR1B1 and AKR1B10 via drug repurposing approach. To assess the drug-like properties of strychnine, a physiologically based pharmacokinetic (PKPB) model and High Throughput Pharmacokinetics (HTPK) approach were employed. The obtained results fell within the expected range for drug molecules, confirming its suitability for further investigation. Additionally, density functional theory (DFT) studies were conducted to gain insight into the electronic properties contributing to the drug molecule's reactivity. Building upon the promising DFT results, molecular docking analysis using the AutoDock tool was performed to examine the binding interactions between strychnine and the proposed targets, AKR1B1 and AKR1B10. Findings from the molecular docking studies suggested a higher probability of strychnine acting as an inhibitor of AKR1B1 and AKR1B10 with docking scores of - 30.84 and - 29.36 kJ/mol respectively. To validate the stability of the protein-ligand complex, Molecular Dynamic Simulation (MDS) studies were conducted, revealing the formation of a stable complex between the enzymes and strychnine. This comprehensive approach sheds light on the potential effectiveness of strychnine as a treatment for breast, lung, liver, and pancreatic cancers, as well as related malignancies. The novel insights gained from the physiologically based pharmacokinetic modeling, density functional theory, molecular docking, and molecular dynamics simulations collectively support the prospect of strychnine as a promising molecule for anticancer therapy. Further investigations are warranted to validate these findings and explore the therapeutic potential of strychnine in preclinical and clinical settings.

Resveratrol-Laden Nano-Systems in the Cancer Environment: Views and Reviews.

The genesis of cancer is a precisely organized process in which normal cells undergo genetic alterations that cause the cells to multiply abnormally, colonize, and metastasize to other organs such as the liver, lungs, colon, and brain. Potential drugs that could modify these carcinogenic pathways are the ones that will be used in clinical trials as anti-cancer drugs. Resveratrol (RES) is a polyphenolic natural antitoxin that has been utilized for the treatment of several diseases, owing to its ability to scavenge free radicals, control the expression and activity of antioxidant enzymes, and have effects on inflammation, cancer, aging, diabetes, and cardioprotection. Although RES has a variety of pharmacological uses and shows promising applications in natural medicine, its unpredictable pharmacokinetics compromise its therapeutic efficacy and prevent its use in clinical settings. RES has been encapsulated into various nanocarriers, such as liposomes, polymeric nanoparticles, lipidic nanocarriers, and inorganic nanoparticles, to address these issues. These nanocarriers can modulate drug release, increase bioavailability, and reach therapeutically relevant plasma concentrations. Studies on resveratrol-rich nano-formulations in various cancer types are compiled in the current article. Studies relating to enhanced drug stability, increased therapeutic potential in terms of pharmacokinetics and pharmacodynamics, and reduced toxicity to cells and tissues are the main topics of this research. To keep the readers informed about the current state of resveratrol nano-formulations from an industrial perspective, some recent and significant patent literature has also been provided. Here, the prospects for nano-formulations are briefly discussed, along with machine learning and pharmacometrics methods for resolving resveratrol's pharmacokinetic concerns.

Effect of Excipients on the Quality of Drug Formulation and Immediate Release of Generic Metformin HCl Tablets.

Generic medications are bioequivalent to brand-name medications, but the quality and purity of generic medications are still debatable. The aim of this study was to compare the generic product of metformin (MET) to its branded counterpart using pure MET powder as a reference. Quality control tablet assessment and in vitro evaluation of drug release were carried out in various pH media. Additionally, several analytical methods and thermal techniques were used, namely differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier-transform infrared (FTIR), and confocal Raman microscopy. The results showed a significant difference between the two products. In terms of friability assessment, mean resistance force, and tablet disintegration, the generic MET product showed significant weight loss, higher mean resistance force, longer disintegration time, and a slower rate of drug release. In addition, DSC and TGA showed that the generic product had the lowest melting point and the least weight loss compared to the branded product and pure powder. XRD and SEM demonstrated some changes in the crystallinity structure of the molecule particles for the generic product. Additionally, FTIR and confocal Raman revealed the same peaks and band shifts in all samples, but with differences in the intensity for the generic tablet only. The observed differences could be due to the use of different excipients in the generic product. The possibility of forming a eutectic mixture between the polymeric excipient and metformin in the generic tablet was presumed, which might be attributed to alterations in the physicochemical properties of the drug molecule in the generic product. In conclusion, using different excipients might have a significant effect on the physicochemical properties of drugs in generic formulations, leading to significant changes in drug release behavior.

Enteric-coating film effect on the delayed drug release of pantoprazole gastro-resistant generic tablets.

Background: Enteric coating films in acidic labile tablets protect the drug molecule from the acidic environment of the stomach. However, variations in the excipients used in the coating formulation may affect their ability to provide adequate protection. This study is the first to investigate the potential effects of coating materials on the protective functionality of enteric coating films for pantoprazole (PNZ) generic tablets after their recall from the market. Methods: A comparative analysis was conducted between generic and branded PNZ products, using pure drug powder for identification. The in vitro release of the drug was evaluated in different pH media. The study also utilized various analytical and thermal techniques, including differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier-transform infrared (FTIR), and confocal Raman microscopy. Results: The in vitro assessment results revealed significant variations in the release profile for the generic product in acidic media at 120 min. DSC and TGA thermal profile analyses showed slight variation between the two products. XRD analysis exhibited a noticeable difference in peak intensity for the generic sample, while SEM revealed smaller particle sizes in the generic product. The obtained spectra profile for the generic product displayed significant variation in peaks and band intensity, possibly due to impurities. These findings suggest that the excipients used in the enteric coating film of the generic product may have affected its protective functionality, leading to premature drug release in acidic media. Additionally, the presence of polysorbate 80 (P-80) in the brand product might improve the properties of the enteric coating film due to its multi-functionality. Conclusions: In conclusion, the excipients used in the brand product demonstrated superior functionality in effectively protecting the drug molecule from acidic media through the enteric coating film, as compared to the generic version.

Polyvinylpyrrolidone K-30-Based Crosslinked Fast Swelling Nanogels: An Impeccable Approach for Drug's Solubility Improvement.

Poor solubility is a global issue of copious pharmaceutical industries as large number of drugs in development stage as well as already marketed products are poorly soluble which results in low dissolution and ultimately dosage increase. Current study is aimed at developing a polyvinylpyrrolidone- (PVP-K30-) based nanogel delivery system for solubility enhancement of poorly soluble drug olanzapine (OLP), as solubilization enhancement is the most noteworthy application of nanosystems. Crosslinking polymerization with subsequent condensation technique was used for the synthesis of nanogels, a highly responsive polymeric networks in drug's solubility. Developed nanogels were characterized by percent entrapment efficiency, sol-gel, percent swelling, percent drug loaded content (%DLC), percent porosity, stability, solubility, in vitro dissolution studies, FTIR, XRD, and SEM analysis. Furthermore, cytotoxicity study was conducted on rabbits to check the biocompatibility of the system. Particle size of nanogels was found with 178.99 ± 15.32 nm, and in vitro dissolution study exhibited that drug release properties were considerably enhanced as compared to the marketed formulation OLANZIA. The solubility studies indicated that solubility of OLP was noticeably improved up to 36.7-fold in phosphate buffer of pH 6.8. In vivo cytotoxicity study indicated that prepared PVP-K30-based formulation was biocompatible. On the basis of results obtained, the developed PVP-K30-co-poly (AMPS) nanogel delivery system is expected to be safe, effective, and cost-effective for solubility improvement of poorly soluble drugs.

Papain-Decorated Mucopenetrating SEDDS: A Tentative Approach to Combat Absorption Issues of Acyclovir via the Oral Route.

The aim of the current study was to enhance the oral bioavailability of Acyclovir (ACV) based on the papain-functionalized self-emulsifying drug delivery systems (SEDDS). The optimum control SEDDS formulation comprised of kolliphore (40%), transcutol (30%), propylene glycol (20%) and oleoyl chloride (10%). However, in the targeted SEDDS formulation, oleoyl chloride was replaced with oleoyl chloride-papain (OC-PAP) conjugate that was synthesized via an amide bond formation between the acyl halide groups of oleoyl chloride and the amino group of papain. Prior to adding in the SEDDS formulation, the newly synthesized conjugate was evaluated quantitatively by a Bradford assay that demonstrated 45 µg of papain contents per mg of the conjugate. Moreover, the conjugate formation was qualitatively confirmed through FTIR analysis and thin layer chromatography. ACV (a BCS class III drug) was incorporated into the SEDDS formulations after being hydrophobically ion paired with sodium deoxycholate, thereby making it lipophilic. The drug-loaded formulations were emulsified in the 0.1 M phosphate buffer (pH 6.8) and evaluated in vitro with respect to drug release and rabbit mucosal permeation studies. Both the formulations illustrated a very comparable drug release over a period of 4 h, afterwards, the OC-PAP-based formulation demonstrated a more sustaining effect. The extent of mucus diffusion evaluated via the silicon tube method demonstrated a 4.92-fold and a 1.46-fold higher penetration of the drug, a 3.21-fold and a 1.56-fold higher permeation through the rabbit intestinal mucus layer, and a 22.94-fold and a 2.27-fold higher retention of the drug over the intact mucosa of rabbit intestine, illustrated by OC-PAP-based nanoemulsions compared to the drug-free solution and controlled nanoemulsion, respectively. According to these in vitro results, papain-functionalized SEDDS is a promising approach for the oral delivery of ACV and many other drugs with oral bioavailability issues, however, in vivo studies in this respect have to be employed before making a comprehensive conclusion.

Pharmacists' knowledge, attitude and practice in the UAE toward the public health crisis of COVID-19: A cross-sectional study.

Objectives: Internationally, pharmacists have shown a pivotal role in alleviating the unprecedented spread of the COVID-19 as they are the first touchpoint to patients. The aim of this study to evaluate the UAE pharmacists' knowledge about and practice in the global COVID-19 pandemic. Methods: A quantitative cross-sectional study was conducted during a period from August 2020 to January 2021. A well-designed standardized English-based questionnaire was developed based on current literature and employed for this study. Findings: The results showed that 45.7% of the participated pharmacists expected to have a good level of knowledge about COVID-19 transmission, symptoms and treatment. Among the participated community pharmacists, around 25.7% educated their patients and 17.0% counseled the public about the current available therapeutic options for managing COVID-19 symptom. Most practiced activities hospital pharmacists (17.4%) was exploring new drug therapies or uses, while few hospital pharmacists (13.0%) participated in the antimicrobial stewardship programs and monitored antibiotic uses for COVID-19 cases and co-infections. Pharmacists at age ≥40 years old and have an experience of ≥10 years in the pharmacy field were more knowledgeable about COVID-19 with higher scores (p <0.001 and p= 0.001; respectively). Conclusions: The study revealed an appropriate average knowledge and practice toward COVID-19 among community and hospital pharmacists.

Pharmacists’ knowledge, attitude and practice in the UAE toward the public health crisis of COVID-19: A cross-sectional study

Objectives: Internationally, pharmacists have shown a pivotal role in alleviating the unprecedented spread of the COVID-19 as they are the first touchpoint to patients. The aim of this study to evaluate the UAE pharmacists’ knowledge about and practice in the global COVID-19 pandemic. Methods: A quantitative cross-sectional study was conducted during a period from August 2020 to January 2021. A well-designed standardized English-based questionnaire was developed based on current literature and employed for this study. Findings: The results showed that 45.7% of the participated pharmacists expected to have a good level of knowledge about COVID-19 transmission, symptoms and treatment. Among the participated community pharmacists, around 25.7% educated their patients and 17.0% counseled the public about the current available therapeutic options for managing COVID-19 symptom. Most practiced activities hospital pharmacists (17.4%) was exploring new drug therapies or uses, while few hospital pharmacists (13.0%) participated in the antimicrobial stewardship programs and monitored antibiotic uses for COVID-19 cases and co-infections. Pharmacists at age ≥40 years old and have an experience of ≥10 years in the pharmacy field were more knowledgeable about COVID-19 with higher scores (p <0.001 and p= 0.001; respectively). Conclusions: The study revealed an appropriate average knowledge and practice toward COVID-19 among community and hospital pharmacists. (AU)

Precise and Sensitive Ambient Temperature Based Analytical Colorimetric Method for Pregabalin

Abstract Pregabalin, a GABA analogue is used to treat epilepsy and neuropathic pain. The drug poses problems in analytical quantification when estimated at a shorter UV wavelength. The expensive and non-repetitive reported analytical methods necessitate the utility and development of an accurate, precise, repetitive, simple and highly sensitive colorimetric method for pregabalin in solution as well as sustained release mini matrices. Pregabalin (having primary amino group) was derivatized at alkaline pH of mixture with optimized ninhydrin solution at ambient temperature (25oC). The ninhydrin-pregabalin derivatized complex (Ruhemann's Purple) was analyzed for drug concentration at absorption maximum (λmax) of 570nm. The linearity was observed in the concentration range of 5-150 µg/mL with coefficient of correlation, 0.998. The developed analytical method was validated according to ICH guidelines and proved to be highly sensitive (LOD 0.917µg/mL, LOQ 3.055µg/mL), with good inter-day as well as intra-day accuracy and precision as 4.65% and 3.75%, respectively. The proposed method was proved to be a simple, sensitive, precise and accurate for the estimation of the minute concentrations of pregabalin in pure form and the developed formulations. Results verified that the proposed method could determine pregabalin at the ambient temperature without requiring high temperatures used in the existing methods. It was concluded that developed method was easier and more suitable for analysis of pregabalin in quality control of commercial preparations

In Vitro and In Vivo Evaluation of Oral Controlled Release Formulation of BCS Class I Drug Using Polymer Matrix System.

Diltiazem hydrochloride is a calcium channel blocker, which belongs to the family of benzothiazepines. It is commonly used to treat hypertension and atrial fibrillation. Even though the drug has high solubility, its high permeability and rapid metabolism in the liver can limit the bioavailability and increase the dose frequencies for up to four times per day. This study focused on a polymer matrix system not only to control the drug release but also to prolong the duration of bioavailability. The polymer matrices were prepared using different ratios of poloxamer-188, hydroxypropyl methylcellulose, and stearyl alcohol. In vitro and in vivo assessments took place using 24 rabbits and the results were compared to commercially available product Tildiem® (60 mg tablet) as reference. Overall, the rate of drug release was sustained with the gradual increase of poloxamer-188 incorporated with hydroxypropyl methylcellulose and stearyl alcohol in the matrix system, achieving a maximum release period of 10 h. The oral bioavailability and pharmacokinetic parameters of diltiazem hydrochloride incorporated in polymer matrix system were similar to commercial reference Tildiem®. In conclusion, the combination of polymers can have a substantial effect on controlling and prolonging the drug release pattern. The outcomes showed that poloxamer-188 combined with hydroxypropyl methylcellulose and stearyl alcohol is a powerful matrix system for controlling release of diltiazem hydrochloride.

Formulation and In-Vitro Characterisation of Cross-Linked Amphiphilic Guar Gum Nanocarriers for Percutaneous Delivery of Arbutin.

Nano-colloidal systems formulated from amphiphilically-modified polysaccharides (degree of modification 16.6%) are focus of prominent study due to their potential to augment active penetration across the skin. Here we report the synthesis of amphiphilically-modified guar gum (GBE-GG) prepared by grafting with glycidol butyl ether (GBE), which were subsequently formed into nanocarriers and loaded with α-arbutin (22.3% loading). The monodispersed and close-to-spherical nanocarriers (size range 239-297 nm) formed via cross-linking were adequately stable mainly at low temperature (4 °C) under physiological pH condition. α-arbutin was released from GBE-GG NPs in a more sustained manner and the release profiles can be accurately represented by the 1st order kinetic model. In-vitro interactions on immortalised human keratinocytes (HaCaT) cells revealed an increase in biological membrane permeability as well as the absence of cellular toxicity at application pertinent concentrations. No substantial haemolytic activity appeared and flow cytometry analysis revealed effective cellular uptake, suggesting their potential as promising nanocarriers for percutaneous delivery that warrants further comprehensive research.

Development and In Vitro Evaluation of Controlled Release Viagra® Containing Poloxamer-188 Using Gastroplus™ PBPK Modeling Software for In Vivo Predictions and Pharmacokinetic Assessments.

Sildenafil is the active substance in Viagra® tablets, which is approved by the FDA to treat sexual dysfunction in men. Poor solubility and short half-life, however, can limit the span of its effectiveness. Therefore, this study focused on an oral controlled release matrix system with the aim to improve solubility, control the drug release, and sustain the duration of drug activity. The controlled release matrices were prepared with poloxamer-188, hydroxypropyl methylcellulose, and magnesium stearate. Various formulations of different ratios were developed, evaluated in vitro, and assessed in silico. Poloxamer-188 appeared to have a remarkable influence on the release profile of sildenafil citrate. In general, the rate of drug release decreased as the amount of polymer was gradually increased in the matrix system, achieving a maximum release period over 12 h. The in silico assessment by using the GastroPlus™ PBPK modeling software predicted a significant variation in Cmax, tmax, t1/2, and AUC0-t among the formulations. In conclusion, the combination of polymers in matrix systems can have substantial impact on controlling and modifying the drug release pattern.

Impact of pharmacist interventions on drug-related problems in general surgery patients: a randomised controlled trial.

OBJECTIVES: The inappropriate use of medications is harmful and is a common issue in hospitalised patients. Patients hospitalised in general surgery wards are usually at high risk for drug-related problems (DRPs). This randomised controlled trial aimed to explore the value of a pharmaceutical care service conducted in general surgery wards in the identification and reduction of DRPs in comparison with standard medical care. METHODS: This study was conducted in general surgery wards including abdominal, cardiovascular, vascular, endocrine, orthopaedic and oncological surgeries at one of the largest teaching hospitals in Jordan over a period of 6 months. Recruited patients were randomised into intervention or control groups. Clinical pharmacists assessed patients' DRPs and submitted recommendations to resolve the identified DRPs in the intervention group. RESULTS: Patients in the intervention group (n=63) and the control group (n=60) had a mean age of 55±14.4 years, with 52.0% being women. A total of 1062 DRPs were identified, with a mean of 8.6±3.6 per patient (intervention group, 8.65±4.2; control group, 8.62±2.6; p=0.56). The commonly identified DRPs included safety (20.2%) and efficacy (19.0%) issues. The acceptance rate for pharmacists' recommendations by physicians was very high (90%) with a good DRP correction rate of 58.9% during patients' hospital stay. The value of pharmaceutical care was significantly reflected in the achievement of the therapeutic outcomes and prevention of morbidity (resolved/improved or prevented) of 68.2% (24.2%+44%) in the intervention group compared with 19.2% (12.4%+6.8%) in the control group (p<0.001). CONCLUSIONS: This study shows that DRPs are common among general surgery patients in Jordan, especially those related to drug safety and efficacy. Pharmacists' recommendations contributed substantially to resolving most of the identified DRPs and had a significant impact on improving medications used in general surgery patients.