In-Silico Assisted Development of Supersaturable Preconcentrated Isotropic Mixture of Atazanavir for Augmenting Biopharmaceutical Performance in Presence of H2-Receptor Antagonist

The therapeutic potential of atazanavir (BCS Class II drug), a highly selective inhibitor of human immunodeficiency virus (HIV-1) has been largely limited due to its low intrinsic solubility at elevated pH resulting in low oral bioavailability. Thus, the current work describes the systematic development, optimization and evaluation of HPMC-AS based supersaturable preconcentrate isotropic mixture (SP-IM) containing long chain triglyceride to improve intestinal lymphatic transport and augment oral bioavailability of atazanavir (ATZ). A D-optimal mixture design was employed for optimization of plain IM containing Corn Oil, Oleic acid, Tween 80 and Propylene Glycol, evaluating CQAs like particle size, PDI, self-emulsification time, % transmittance and drug content. In-silico analysis and in-vitro supersaturation test facilitated the selection of HPMC-AS as a best suited polymeric precipitation inhibitor (PPI) for formulating ATZ loaded SP-IM (ATZ-SP-IM). In-vitro dissolution data indicated that ATZ-SP-IM exhibits superior performance in 0.025N HCl and pH 6.8 over pure drug. Ex-vivo permeation and in-vivo pharmacokinetic study of ATZ-SP-IM corroborated enhanced permeation (2.03 fold) and improved drug absorption via lymphatic transport in wistar rats. Further, the pharmacokinetic performance of ATZ-SP-IM was not affected in presence of H2 receptor antagonist. Therefore, the results showed that ATZ-SP-IM can significantly improve the biopharmaceutical attributes of ATZ so as to lay a foundation of further research on the new dosage form of ATZ.

Effect of famotidine on hospitalized patients with COVID-19: A systematic review and meta-analysis

Introduction Famotidine is a competitive histamine H2-receptor antagonist most commonly used for gastric acid suppression but thought to have potential efficacy in treating patients with Coronavirus disease 2019 (COVID-19). The aims of this systematic review and meta-analysis are to summarize the current literature and report clinical outcomes on the use of famotidine for treatment of hospitalized patients with COVID-19. Methods Five databases were searched through February 12, 2021 to identify observational studies that reported on associations of famotidine use with outcomes in COVID-19. Meta-analysis was conducted for composite primary clinical outcome (e.g. rate of death, intubation, or intensive care unit admissions) and death separately, where either aggregate odds ratio (OR) or hazard ratio (HR) was calculated. Results Four studies, reporting on 46,435 total patients and 3,110 patients treated with famotidine, were included in this meta-analysis. There was no significant association between famotidine use and composite outcomes in patients with COVID-19: HR 0.63 (95% CI: 0.35, 1.16). Across the three studies that reported mortality separated from other endpoints, there was no association between famotidine use during hospitalization and risk of death—HR 0.67 (95% CI: 0.26, 1.73) and OR 0.79 (95% CI: 0.19, 3.34). Heterogeneity ranged from 83.69% to 88.07%. Conclusion Based on the existing observational studies, famotidine use is not associated with a reduced risk of mortality or combined outcome of mortality, intubation, and/or intensive care services in hospitalized individuals with COVID-19, though heterogeneity was high, and point estimates suggested a possible protective effect for the composite outcome that may not have been observed due to lack of power. Further randomized controlled trials (RCTs) may help determine the efficacy and safety of famotidine as a treatment for COVID-19 patients in various care settings of the disease.

Evaluasi Penggunaan Obat Gangguan Saluran Cerna pada Pasien Rawat Inap berdasarkan Formularium Nasional di Faskes Tingkat Pertama

Gangguan pencernaan merupakan masalah yang terjadi pada salah satu organ sistem pencernaan, atau lebih dari satu organ pencernaan secara bersamaan. Gangguan saluran cerna yang sering dijumpai di sekitar masyarakat adalah gastroenteritis, dispepsia, gerd dan diare. Penelitian ini menggunakan metode kualitatif deskriptif. Peneliti menggunakan Indikator penggunaan obat yaitu tepat diagnosa, tepat indikasi, tepat dalam pemilihan obat, tepat dosis, efek samping, interval pemerian, dan tepat waktu. Penggunaan obat yang tepat harus disesuaikan dengan formularium yang disusun oleh petugas fasilitas kesehatan untuk memaksimalkan pelayanan kesehatan kepada masyarakat. Hasil penelitian menunjukan bahwa Terdapat 52,5% tenaga medis yang merasa kurang paham terhadap formularium nasional karena berbagai faktor dari mulai rasa ingin tahu yang kurang atau petugas kefarmasian yang tidak melakukan sosialisasi kepada nakes lainya, dan 30% nakes menjawab paham terhadap formularium nasional dan 17,5% menjawab tidak paham. Pengawasan terhadap pasien rawat inap dengan gangguan saluran cerna di faskes tingkat pertama sangat baik, petugas kefarmasian menggunakan form ceklis untuk melihat tingkat kerasionalan penggunaan obat dan indikator peresapan fornas. Tersedianya obat golongan PPI (proton pump inhibitor) yaitu omeprazole 40mg cap dan golongan Histamin H2-receptor antagonist yaitu ranitidin tablet dan ranitidin sediaan injeksi juga antiemetika sediaan tablet dan sirup yaitu domperidon dan obat tersebut merupakan obat-obat yang harus ada di faskes tingkat pertama.

The Effect of Famotidine on Hospitalized Patients with COVID-19: a Systematic Review and Meta-Analysis

Introduction: Famotidine is a competitive histamine H2-receptor antagonist most commonly used for gastric acid suppression but thought to have potential efficacy in treating patients with COVID-19. The aims of this systematic review and meta-analysis are to summarize the current literature and report clinical outcomes on the use of famotidine for treatment of hospitalized patients with COVID-19. Methods: Five databases were searched through February 12, 2021 to identify observational studies that reported on associations of famotidine use with outcomes in COVID-19. Meta-analysis was conducted for composite primary clinical outcome (e.g. rate of death, intubation, or intensive care unit admissions) and death separately, where either aggregate odds ratio (OR) or hazard ratio (HR) was calculated. Results: Four studies, reporting on 46,435 total patients and 3,110 patients treated with famotidine, were included in this meta-analysis. There was no significant association between famotidine use and composite outcomes in patients with COVID-19: HR 0.63 (95% CI: 0.35, 1.16). Across the three studies that reported mortality separated from other endpoints, there was no association between famotidine use during hospitalization and risk of death - HR 0.67 (95% CI: 0.26, 1.73) and OR 0.79 (95% CI: 0.19, 3.34). Heterogeneity ranged from 83.69% to 88.07%. Conclusion: Based on the existing observational studies, famotidine use is not associated with a reduced risk of mortality or combined outcome of mortality, intubation, and/or intensive care services in hospitalized individuals with COVID-19, though heterogeneity was high, and point estimates suggested a possible protective effect for the composite outcome that may not have been observed due to lack of power. Further RCTs may help determine the efficacy and safety of famotidine as a treatment for COVID-19 patients in various care settings of the disease

Famotidine Repurposing for Novel Corona Virus Disease of 2019: A Systematic Review

Background COVID-19 caused by SARS-CoV-2 was declared as a global pandemic by the WHO. Famotidine is a histamine-2 (H2) receptor antagonist which blocks the H2 receptors in the parietal cells, decreasing gastric acid secretion. Our review aims to study all the available scientific evidence on famotidine research outcomes systematically to introspect its clinical efficacy and probable mechanisms and clinical efficacy against SARS-CoV-2. Methodology An electronic search of PubMed, Scopus and Google Scholar was performed using MeSH terms “SARS CoV-2” OR “COVID-19” AND“FAMOTIDINE”. Relevant informationwas extracted from studies reporting the efficacy of famotidine in COVID-19. Results We found a total of 32 studies, out of which only 14 were relevant and were included in our review.Molecular computational studies showed that famotidine selectively acts on viral replication proteases papain-like protease (PLpro) and 3-chymotrypsin-like protease (3CLpro). Additionally, it acts via inverse-agonism on the H2 receptors present in neutrophils and eosinophils which leads to inhibition of cytokine release. Clinical study findings have pointed toward significant improvements in COVID-19 patient-reported symptoms in non-hospitalized patients and reduction in intubation or death in critically ill patients associated with the usage of famotidine. However,in one of the studies,famotidine has failed to show any significant benefit in reducing mortality due to COVID-19. Conclusion Famotidine has the potential to answer the ongoing global challenge owing to its selective action on viral replication. Additionally, clinical findings in COVID-19 patients support its efficacy to reduce clinical symptoms of COVID-19.We suggest that further optimally powered randomized clinical trials should be carried out to come up with definitive conclusions.

A STUDY ON DRUG-DRUG INTERACTION BETWEEN GLIPIZIDE AND CIMETIDINE IN RABBITS

Objective: To study the effect of Cimetidine (H2 receptor antagonist) in combination with Glipizide (Sulfonylurea) on the blood sugar level in rabbits. Methods: Six albino rabbits were taken for the study. Glipizide was administrated to each rabbit as a single drug therapy on day 1 and it was co-administrated with Cimetidine to each rabbit as a combinational drug therapy on day 7. Cimetidine was administrated to each rabbit from day 2 to day 6 as single drug therapy. Blood sugar levels were estimated on day 1 and on day 7 at 0, 1, 2, 4, and 6 h. Results: The mean blood sugar level readings at 0, 1, 2, 4 and 6 h on day 1 were 90.4, 69.4, 62.9 and 65.7 mg% and on day 7 were 89.4, 74.8, 65.5, 56.4 and 61.2 mg % respectively. When mean blood sugar level on day 1 and day 7 was considered, there was a significant reduction in blood sugar level at 1, 2, 4 and 6 h and there was no significant fall in blood sugar level at 0 hour after co-administration of Glipizide and Cimetidine. Conclusion: Cimetidine, when co-administered with Glipizide, significantly increases the hypoglycaemic action of Glipizide.

Analytical method development and validation studies for the estimation of H2 receptor antagonist drug (Ranitidine)

<p class="abstract"><strong>Background:</strong> An analytical science in the development, finding a new molecules and procreation of pharmaceuticals has been an extensive approached. From the evaluation over small quantities of complex biological substances to the quality monitoring of the finished dosage form, the use on analytical technology know- how covers an ample thoroughness over techniques or disciplines.</p><p class="abstract"><strong>Methods:</strong> Reversed phase high performance liquid chromatography (RP-HPLC) approach has been promoted for the discernment over Ranitidine (RAN) within pharmaceutical dosage form split of RAN was accomplished inside a unaccompanied chromatographic run of an Phenomenix column size 5 μm 4.6x250 mm along with UV analysis at 227 nm wavelength, below isocratic conditions, using Ammonium acetate and Methanol (pH 6.0) in 80:20 ratio. Validation parameters had been observed in accordance with exhibit linearity, accuracy, precision, Limit of Quantitation and Limit of detection in conformity in imitation of ICH guidelines. </p><p class="abstract"><strong>Results:</strong> The contemporary approached demonstrates significant linearity upon the range concerning 50-202.5 μg/ml for RAN followed by intra-day and inter-day precision, expressed so the relative standard deviation (RSD), on replicates is &lt;2.0 and accuracy among the range over 98-102%.</p><p class="abstract"><strong>Conclusions:</strong> The flourished RP-HPLC technique was once innovative, suitable for detecting RAN in pure form and in pharmaceutical preparation.</p>