Comparison of Hydroxypropylcellulose and Hot-Melt Extrudable Hypromellose in Twin-Screw Melt Granulation of Metformin Hydrochloride: Effect of Rheological Properties of Polymer on Melt Granulation and Granule Properties

High-molecular-weight hypromellose (HPMC) and hydroxypropyl cellulose (HPC) are widely known, extended-release polymers. Conventional high-molecular-weight HPMCs are preferred in extended-release applications but not widely used in twin-screw melt granulation due to processability difficulties at low operating temperatures and potential drug degradation if high processing temperatures are used. Conversely, high-molecular-weight grade HPC (Klucel®) can be used in melt granulation processes. The purpose of this study was to evaluate the processability and dissolution behavior of HPC GXF ((Klucel® GXF) and a recently introduced type of hot-melt extrudable HPMC (Affinisol®) in extended-release metformin hydrochloride formulations using twin-screw melt granulation. Powder blends were prepared with 75% w/w metformin HCl and 25% w/w polymeric binder. Blends were granulated at processing temperatures of 160, 140, 120 and 100 °C. HPMC HME 4M (Affinisol® 4M) provided a fine powder, indicating minimum granulation at processing temperatures lower than 160 °C, and the tablets obtained with these granules capped during tableting. In contrast, acceptable tablets could be obtained with HPC GXF at all processing temperatures. Rheological studies including capillary rheometry to measure steady shear rate viscosity, and rotational rheometry to obtain time and temperature superposition data, showed that HPC GXF had a greater thermoplasticity than HPMC HME 4M, which made granulation possible with HPC GXF at low temperatures. Tablets compressed with granules obtained at 160 °C with both binders showed comparable dissolution profiles. High-molecular-weight HPC GXF provided a better processability at low temperatures and adequate tablet strength for the melt granulation of metformin HCl.

Validation of Analytical Methods for Tacrolimus Determination in Poly(ε-caprolactone) Nanocapsules and Identification of Drug Degradation Products

The aim of this paper was to use chromatographic tools for validating an analytical method for the tacrolimus (TAC) determination in polymeric nanocapsules and for identifying the drug degradation products after alkaline stress. A rapid Ultra-High-Performance Liquid Chromatography coupled with photo-diode array (UHPLC-PDA) method was successfully performed using the following chromatographic conditions: the Shimadzu Shim-pack XR-ODS III C18 column (100 mm×2.00 mm, 2.2 μm), the mobile phase consisting of methanol and acidified ultrapure water (89:11 v/v), the flow rate of 0.55 mL·min−1, and the ultraviolet (UV) detection at 235 nm. This method was validated as per International Council for Harmonisation (ICH) guidelines. In addition, a TAC forced degradation assay was carried out after alkaline stress and its degradation products were investigated using Liquid Chromatography coupled tandem mass spectroscopy (LC-MS/MS). The calibration curve was linear in the range of 100.0–300.0 μg·mL−1 (r >0.9999). Accuracy was confirmed by the TAC recovery of 96.55 to 98.19%. Precision (intraday and interday) were demonstrated by relative standard deviation lower than 0.89% and 3.25%, respectively. Selectivity and robustness were also proved. The method developed it was successfully applied to quantify TAC from polymeric nanocapsules, showing a high loading efficiency rate (>96.47%). The main drug degradation product observed in a multiple reaction monitoring (MRM) experiment was m/z 844, confirming the susceptibility of TAC under alkaline conditions; this finding was first time described.

IDENTIFICATION OF PUBLIC MEDICINE STORAGE PROFILE IN THE COMMUNITY PHARMACY: A SYSTEMATIC REVIEW

Background: Drug is the most common form of therapy and an integral part of almost all levels of care. The conditions and proper way of storing medicines at home are important aspects of safe and effective drug treatment. Information about the knowledge of patients with appropriate storage conditions, rational drug use, appropriate drug use and management of various drugs is essential in helping pharmacists identify which medicinal products and aspects of home storage require more attention when counselling patients. Objective: The aim of this systematic review is to identify and characterize the mode of storage associated with home-stored pharmaceuticals. Methods: This systematic review analyzes the storage methods for medicines to identify and characterize the storage methods associated with medicines stored at home. The limitation of publication used, namely English and Indonesian in the last 10 years, and obtained through literature that can be considered relevant. Results: This systematic review was conducted in the period July, August, September 2020 - February 2021. As many as 20 journals were obtained. Those who met the inclusion criteria were 10 journals. Of the 10 journals that had met the inclusion criteria, 3 journals were excluded so that only 7 journals were used in the literature review / systematic review. The storage of medicines in the household is based on the presence of family members who have certain diseases so that they have to consume drugs in the long term, the presence of health workers, and the education level of family members. Problems that can arise with drug storage conditions are impaired drug stability and can accelerate drug degradation prematurely. Storage of medicines in the medicine cabinet and out of reach of children is highly recommended. Placement of drugs in one place without being separated and a lack of awareness in administering specific markings can increase drug administration errors and lead to non-compliance with over-the-counter drug use. The application of drug management in the family can improve the quality of life and avoid the adverse effects of drug misuse. Conclusion: This study raises relation to medicines stored inside homes that warrant addressing that need pharmacists regarding public education in relation to drug therapy that goes beyond the dispensing process. They were judging by the finding that pharmacists were not considered primary sources of drug-related information. Good practices should be encouraged through continued health education at health institutions and retail medicine outlets. Keywords: Drugs, Storage, Household

Effects of ex vivo Extracorporeal Membrane Oxygenation Circuits on Sequestration of Antimicrobial Agents

Objectives: Our ex vivo study was designed to determine the sequestration of teicoplanin, tigecycline, micafungin, meropenem, polymyxin B, caspofungin, cefoperazone sulbactam, and voriconazole in extracorporeal membrane oxygenation (ECMO) circuits.Methods: Simulated closed-loop ECMO circuits were prepared using 2 types of blood-primed ECMO. After the circulation was stabilized, the study drugs were injected into the circuit. Blood samples were collected at 2, 5, 15, 30 min, 1, 3, 6, 12, and 24 h after injection. Drug concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry. Control groups were stored at 4°C after 3, 6, 12, and 24 h immersing in a water bath at 37°C to observe spontaneous drug degradation.Results: Twenty-six samples were analyzed. The average drug recoveries from the ECMO circuits and control groups at 24 h relative to baseline were 67 and 89% for teicoplanin, 100 and 145% for tigecycline, 67 and 99% for micafungin, 45 and 75% for meropenem, 62 and 60% for polymyxin B, 83 and 85% for caspofungin, 79 and 98% for cefoperazone, 75 and 87% for sulbactam, and 60 and 101% for voriconazole, respectively. Simple linear regression showed no significant correlation between lipophilicity (r2 = 0.008, P = 0.225) or the protein binding rate (r2 = 0.168, P = 0.479) of drugs and the extent of drug loss in the ECMO circuits.Conclusions: In the two ECMO circuits, meropenem and voriconazole were significantly lost, cefoperazone was slightly lost, while tigecycline and caspofungin were not lost. Drugs with high lipophilicity were lost more in the Maquet circuit than in the Sorin circuit. This study needs more in vivo studies with larger samples for further confirmation, and it suggests that therapeutic drug concentration monitoring should be strongly considered during ECMO.

A Mini-Review on Chitosan Microsphere Drug Delivery

The study aims to determine the drug therapy of any disease to attain the desired therapeutic concentration of the drug in plasma or at the site of action and maintain it for the entire duration of treatment. A drug on being used in conventional dosage forms leads to unavoidable fluctuations in the drug concentration leading to under medication or overmedication and increased frequency of dose administration as well as poor patient compliance. To minimize drug degradation and loss, to prevent harmful side effects and to increase drug bioavailability various drug delivery and targeting systems are currently under development. Handling the treatment of severe disease conditions has necessitated the development of innovative ideas to modify drug delivery techniques. Drug carrier systems include polymers, micelles, microcapsules, Liposomes and lipoproteins etc. Different polymer carriers exert different effects on drug delivery. Synthetic polymers are usually no biocompatible, non-biodegradable and expensive. Natural polymers such as chitin and chitosan are devoid of such problems. Chitosan is a biocompatible, biodegradable, and nontoxic natural polymer with excellent film-forming ability. Being of cationic character, chitosan is able to react with polyamines giving rise to polyelectrolyte complexes. Hence chitosan has become a promising natural polymer for the preparation of microspheres or nanospheres and microcapsules. This review focuses on the preparation, characterization of chitosan microspheres and their role in novel drug delivery systems. This review also aims to include the process variables factors that affect the release of drugs from the microspheres.

Direct Detection of Beta-Lactamase Mediated Antibiotic Resistance In Clinical Specimens

Antibiotic resistance mediated by beta-lactamase enzyme expression is a serious and growing threat. The typical workflow in a clinical microbiology lab leading to identification of beta-lactamase expressing organisms typically requires 48 to 72 hours and involves multiple manual steps. Empiric treatment with potentially ineffective antibiotics often occurs before susceptibility testing results are available. Objective: The objective of our study was to determine if beta-lactamase activity could be detected in clinical urine samples to provide same-day rule-out of select empiric treatment regimens for urinary tract infections. Methods: We acquired urine samples from 40 patients with extended spectrum beta-lactamase expressing (ESBL) infections and 100 patients without ESBL infection as determined by standard culture and sensitivity methods. These samples were incubated with spiked beta-lactam antibiotics susceptible to ESBL degradation (ceftriaxone, cefazolin, and oxacillin) or resistant to ESBL degradation (meropenem). Results: Hydrolysis of spiked drug was detected after a 4 hour incubation with either liquid-chromatography mass-spectrometry (LC-MS) or matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) methods. A 100 to 1000 fold reductions in measured concentrations of spiked ceftriaxone, cefazolin, or oxacillin were observed with LC-MS or MALDI-TOF methods for all 40 ESBL containing specimens and unchanged concentrations of spiked drug were observed in all 100 non-ESBL containing specimens. Concentration of spiked meropenem (resistant to ESBL degradation) were unchanged in all specimens after incubation regardless of ESBL status. Addition of a beta-lactamase inhibitor prevented ESBL degradation of ceftriaxone, cefazolin, and oxacillin demonstrating that beta-lactamase activity (and not another method of drug degradation or signal masking) is being detected. Incubation times as long as 24 hours (to determine method specificity) and as short as 30 minutes (to determine method sensitivity) all showed robust discrimination between ESBL-containing and non-ESBL containing specimens. Conclusion: Our results demonstrate that beta-lactamase activity can be robustly detected in urine samples days before culture and susceptibility results could be available. Clinical utilization of the assay described would enable clinicians to reduce ineffective empiric treatment of ESBL urinary infections.

PREVENTIVE AND CURATIVE ASPECT OF DHUMNASYA (NASAL INSUFFLATION OF MEDICATED SMOKE)

Background- Panchkarma is a group of procedures known for its preventive, promotive, prophylactic and rejuve- nating properties as well as radicle cure. Nasya is one of the Panchkarma treatments. Among the various forms of Nasya, Dhumnasya is a very effective type of Nasya which has further been classified into different types based on various potency of herbs with their respective properties. Aim and Objective: To find out the role of Dhumnasya in the preventive and curative aspects. Material and Methods: Classics of Ayurveda having references regarding Nasya, Modern literature, published articles in peer-reviewed journals, published books and subject-related material available online have been screened, compiled, organized and described systematically. Result: In Dhumnasya medicinal herbs with other constituents are burnt in such an effective manner to produce a medicated fume contain- ing volatile phytochemical of herbs, which when inhaled through nasal route exerts their efficient role in both pre- vention and treatment of various forms of disease both at a local and systemic level. Conclusion: In this review article, it has been tried to focus on the preventive and curative aspect of Dhumnasya so to help to address issues related to poor bioavailability, slow absorption, drug degradation and adverse event in the GIT tract and avoid the first-pass metabolism in the liver and discover the advantage of smoke based therapies as rapid delivery to the brain, more efficient pulmonary absorption and become the suitable substitute for the oral and parental administration. Keywords: Panchkarma, Dhumnasya, Nasya, Medicated smoke.

Nanostructured Lipid Carriers for the Formulation of Topical Anti-Inflammatory Nanomedicines Based on Natural Substances

The main function of the skin is to protect the body from the external environment. However, the skin can undergo inflammatory processes, due to genetic, hormonal, or environmental factors. When the defense system is overloaded, there is an increase in pro-inflammatory mediators and reactive oxygen species (ROS), which results in skin disorders. Among the substances used to treat these inflammatory processes, many natural substances with anti-inflammatory and antioxidant properties are being studied: nature is yet an abundant source to obtain diverse pharmacological actives. The treatment of skin diseases is usually focused on topical application, as it reduces the risk of systemic side effects and prevents drug degradation by first-pass metabolism. Thus, the properties of drug delivery vehicles can facilitate or inhibit its permeation. Due to the hydrophobic nature of the skin, a promising strategy to improve dermal drug penetration is the use of lipid-based nanoparticles, such as nanostructured lipid carriers (NLC). Therefore, in this review, we present NLC as a tool to improve dermal administration of natural substances with anti-inflammatory properties.

Dissolution and Dissolution Test Apparatus: A Review

Dissolution is an official test. These used by pharmacopeias for evaluating drug release of solid and semisolid dosages forms. The application of the dissolution testing ensures consistent product quality and to predict in vivo drug bioavailability. The dissolution test, in its simplest form, placing the formulation in a dissolution apparatus containing suitable dissolution medium, allowing it to dissolved specified period of time and then using appropriate rational method to determine the amount of drug. Dissolution test are probative and analysis like drug degradation profile, shelf-life studies, stability, physical and mechanical testing of dosage forms. The present review outlines findings on various dissolution apparatus, various methods and their modification. Dissolution testing the of various dosage form like Delayed release dosage form, Immediate release dosage form, Extended-release dosage form, Powders, Chewable tablets, Transdermal delivery system, Buccal tablets, Soft gelatin capsule, Chewing gums, Suppositories, Aerosols and others semisolids. This article goal of the description of the all-official dissolution testing apparatus.