Current Drug Therapy - Volume 14, Issue 3, 2019

Ramelteon is a melatonin receptor agonist that is approved for the treatment of insomnia. It is widely used due to its relatively benign side effect profile and lack of dependence or withdrawal. Due to its tolerability, clinicians have attempted to utilize ramelteon to normalize the sleep/wake patterns in patients with delirium as a safer alternative to antipsychotics or other medications. We present the case of a 75-year-old man with long-standing dementia who was hospitalized due to mental status changes, agitation, and sleep disturbance. After addressing possible underlying causes with minimal improvement, the team initiated treatment with ramelteon (8mg nightly) which resulted in rapid improvement of symptoms. Uses and mechanisms of action of ramelteon will be reviewed, as well as current pharmacologic treatments of delirium. Prior research studies and case reports regarding the use of ramelteon in the treatment of delirium will be discussed and suggestions made regarding possible areas of future study.

Transdermal drug delivery systems (TDDS) are one of the fascinating unconventional drug delivery systems offering plentiful advantages of which patient compliance is of paramount importance. However, as a matter of fact, the transdermal delivery of drug molecules is absolutely a tedious job which is precisely influenced by a number of factors including penetration barrier properties of the skin, drug characteristics formulation allied issues, etc. Over the years, innumerable tremendous efforts have been made in transporting the drugs through the skin into the systemic circulation by noteworthy tactics. This paper discusses such revolutionary formulation based techniques that have been endeavored in achieving the enhanced skin permeation of drugs, controlled release, and safety.

Background: Second generation direct acting-antivirals are safe and effective treatments for chronic hepatitis C patients. Objective: We aimed to conduct a systematic review of case reports and case series to evaluate the safety of the drugs, highlighting a compilation of AE not previously reported in other reviews. Methods: The search was performed in four electronic databases and included only case reports and case series that evaluated interferon-free therapies and provided safety outcomes. Results: Initially 1,235 records were retrieved, and after screening 30 studies were included in the analysis (23 case reports and 7 case series). A total of 39 patients were included, receiving eight different interferon-free treatments. Nineteen patients discontinued treatment (only 8 of these achieved treatment response). Other 19 patients achieved SVR without discontinuation. Rare adverse events were observed, including breast hypertrophy, retinopathy and drug-induced infection. Some patients were in an advanced stage of the disease, and were therefore unable to withstand treatment due to the appearance of complications. Conclusion: In this sense, it is important to monitor the use of these drugs that can favor the appearance of serious AE. (PROSPERO registration number CRD42016051680).

Background: At present, the interpretation of any dysfunction by pathogenic microbial colonization of the digestive tract can be considered as the rupture of the microbiotic balance in the injured or infected area. Phytodrugs with useful properties to balance the intestinal microbiota equibiotics represent an alternative recently proposed by the Medicinal Plant Research Company Phytomedicamenta S.A. The Equibiotic-GI® is a phytodrug developed as a combination of two plant extracts, obtained from the leaves of Psidium guajava L, (Myrtaceae) and the roots of Coptis chinensis Franch. (Racunculaceae). Both plants used traditionally for the treatment of several gastrointestinal disorders. Objective: The aim of the current study was to assess the effect of Equibiotic-GI® suspension on intestinal microbiota of subjects with functional dyspepsia. Methods: An open-label study performed in 8 adult subjects with functional dyspepsia receiving orally 20 mL of the suspension, daily for two weeks. Fecal samples were collected at baseline and the end of treatment for assessing gut microbiota composition by sequencing the V3-V4 region of the 16S rRNA gene. Results: Equibiotic-GI modified the Bacteriodetes/Firmicutes proportion increasing the richness of the microbiota composition and Rikenellaceae and Alistipes abundance. Conclusion: Together with the improvement in the gastrointestinal symptomatology after the consumption of the product, the present study is the first clinical demonstration of the capacity of the Equibiotic-GI® to restore and balance the intestinal microbiota.

Background: Tuberculosis is a major public health problem in the world. Isoniazid is a first line antitubercular drug active against Mycobacterium species which inhibits mycolic acid synthesis. Objective: The aim of the present investigation was the preparation of solid lipid nanoparticle containing Isoniazid to increase bioavailability, sustained release and decrease toxicity by increasing permeability. Methods: Isoniazid was incorporated into SLN for sustained drug delivery, increasing permeability and bioavailability. SLNs were prepared by emulsification followed by the solvent evaporation technique by optimizing lipid, polymer and surfactant ratio under controlled optimized process variables i.e. temperature and stirring speed. SLNs were characterized for particle size analysis, comparative study design in different physiological pH for in-vitro drug release and drug release kinetics. Results: The best in-vitro release for F7 was found to be 80.2% in pH-7.4 and 82.2% in pH-4.5. The particle size of the F7 formulation was found to be in the range of 200- 600nm . Among all 3 optimized formulations, i.e. F3, F7 and F8 in both the pH, F3 followed non-fickian diffusion mechanism in pH-4.5 whereas all the formulations in both pH followed super-case II diffusion mechanism. The stability studies were carried out as per ICH guidelines which signify that the SLNs were found stable in the refrigerated condition. Conclusion: The results clearly demonstrated that SLNs drug delivery system is a promising approach for antitubercular drug delivery as it proved to sustained release, increase permeability, enhanced bioavailability and thus decreased dosing frequency. Kinetic modelling of the formulation with zero, first order, Higuchi and Korsmeyer- peppas is explained in this article.

Background: Targeting anti-tubercular therapeutics to alveolar macrophages using microparticles technology mainly focuses on increasing local concentrations of therapeutics and potentially reducing the frequency of dosing requirements. Rifampicin (RIF), Ofloxacin (OFX) and Ethambutol (ETH) combination show synergism. Objective: In light of the above facts, the focus of the present study was to develop and characterize novel Dry powder Inhaler formulation incorporating novel drug combination as a pulmonary delivery for the effective eradication of Tuberculosis. Method: Biodegradable microparticles containing RIF, OFX and ETH were prepared by a spray drying technique using PLGA polymer through the critical process as well as polymer attributes were screened and optimized using 2³ factorial design. The identified critical process parameters (CPP’s) viz. Inlet temperature, Aspiration rate, and feed rate were selected as independent variables while percentage yield, percentage entrapment efficiency, and particle size were selected as a response. The formulated microparticles were evaluated for particle size, drug-polymer compatibility study, aerodynamic behavior, morphology, particle size distribution, crystallinity, residual solvent content, in-vitro drug release study, and stability study. Results: By choosing the optimum spray drying conditions maximum yield of 73%, entrapment efficiency of 86% and particle size of 1.4 μm was attained of the optimized batch. Thus the results revealed that spherical microparticles are suitable for inhalation and sustained release for 12 h. Conclusion: The successful formulation and evaluation of dry powder could be used as an enhanced therapeutic alternative of the standard oral anti-tubercular regimen, rescuing oral dosing, shortening drug regimen and limiting toxicity. This will ultimately improve patient compliance and diminish the prevalence of MDR resistance.

Background: A prescription study is an effective method to evaluate irrational prescribing practice. Hypertension is one such major chronic disease. Compliance to guidelines like the JNC-8 (Eighth Joint National Committee) and Saudi Hypertension guidelines is highly recommended to prevent future complications. Objective: We conducted this study to assess prescribing pattern and their compliance with the guidelines in the patients. Methods: A Retrospective cross-sectional study was carried out for 7 weeks in 2017 in Aseer region, Abha, Saudi Arabia on 122 outpatient prescriptions which were included by Non-probability convenience sampling technique. Data from patients aged above 18 years with any stage of Hypertension with or without Diabetes Mellitus was collected. Results: It was found that Angiotensin converting enzyme inhibitors were frequently prescribed as monotherapy in patients with Hypertension with or without Diabetes Mellitus which is in compliance to the guidelines. Beta-blockers were most commonly used in 2 and 3 drug therapy of patients with only Hypertension which was not in accordance with the guidelines. Conclusion: By this it could be concluded that the Prescription pattern of Antihypertensive in Aseer Region was in compliance with both the guidelines to a partial extent. Though most of the prescriptions were rational, further improvement was required. Studies that focus on demographic data, economic status, associated conditions and complications would give additional insights into prescribing patterns in hypertension.