Clozapine-carboxylic acid plasticized co-amorphous dispersions: Preparation, characterization and solution stability evaluation

This study addressed the possibility of formating of co-amorphous systems between clozapine (CZ) and various carboxylic acid plasticizers (CAPs). The aim was to improve the solubility and oral bioavailability of clozapine. Co-amorphous dispersions were prepared using modified solvent evaporation methodology at drug/plasticizer stoichiometric ratios of 1:1, 1:1.5 and 1:2. Solid state characterization was performed using differential scanning calorimetry, X-ray diffraction and infra red spectroscopy. Highly soluble homogeneous co-amorphous dispersions were formed between clozapine and CAPs via hydrogen bonding. The co-amorphous dispersions formed with tartaric acid (1:2) showed the highest dissolution percentage (> 95 % in 20 minutes) compared to pure crystalline CZ (56 %). Highly stable solutions were obtained from co-amorphous CZ-citric and CZ-tartaric acid at 1:1.5 molar ratio. The prepared dispersions suggest the possibility of peroral or sublingual administration of highly soluble clozapine at a reduced dose with a great chance to bypass the first pass metabolism

COVID-19 is Associated with Increased Severity in Pregnant Women

Background: COVID-19 pandemic originated in China in late 2019, the number of cases are increasing with 2,104,346 cases and 116,140 deaths in the United States, as of June 16, 2020. Pregnant women are a vulnerable population in epidemics or Pandemics. This Review is designed to look in detail the severity of COVID-19 in pregnant women in comparison to non-pregnant women of reproductive age. Methods: Literature search on PubMed, Google Scholar, Lancet, and Web of Science were conducted. Results: We have found the evidence of increased risk for severe disease and distinctive symptoms among pregnant women diagnosed with COVID-19 as compared to non-pregnant women. Conclusions: COVID-19 presents in an atypical fashion in pregnant women with comparatively increased severity of symptoms, compared to COVID-19 positive non pregnant women of reproductive age. These findings can help clinicians to recognize the risk posed by COVID-19 in pregnant women

COVID-19 & Pregnancy Complication During Early Pandemic: A Narrative Review

Background: Coronaviruses have caused 3 outbreaks in the past 2 decades. The novel one is SARS-COV-2, which causes COVID-19. Pregnant women have somewhat altered immune state, which may make them more vulnerable to COVID-19 and its complications. Extensive research is needed to better understand the clinical course of COVID-19 in this population. Objective: This review article discusses the comparison of previous coronaviruses’ outbreaks, clinical presentations, and complications in pregnant women and newborns. Study Design: We conducted literature search for case series and case reports about pregnancy outcomes in pregnant women with COVID-19 during the early phase of pandemic. Results: In case series, 37 of 129(28.6%) pregnant women with COVID-19 disease had preterm delivery and 14 of 67 pregnant women had fetal distress. The rate of preterm labor in normal pregnant women who are healthy and not infected with any virus worldwide is approximately 11%. Conclusion: Based on the articles reviewed, preterm delivery appears to be the most common complication in COVID-19 pregnant patients. Other complications include fetal distress, stillbirth, ICU admission and severe disease leading to fetal demise and maternal mortality. Pregnancy outcomes seem to be better with Covid-19 compared to SARs and MERS. However, most of these publications are from the early part of the pandemic when protocols for care for pregnant women were being worked out and comprehensive knowledge of the disease process in pregnant women was still in developing stage

Comparative Pharmacokinetic Study of Two Lyophilized Orally Disintegrating Tablets Formulations of Vinpocetine in Human Volunteers

Vinpocetine is a poorly water soluble drug, commonly used in treatment of various cerebral insufficiency conditions. The aim of this work was to formulate vinpocetine in the form of orally disintegrating tablets (ODTs) and enhance its solubility and dissolution rate. This objective was addressed using lyophilization technique of either solid dispersion using polyethylene glycol 4000 (PEG 4000) or inclusion complex with 2-hydroxypropyl β-cyclodextrin (2HP-β-CD). Differential scanning calorimetry (DSC) and fourier transform-infrared (FT-IR) spectroscopy were used to characterize the solid state of the prepared solid complex. Tablets were prepared by direct compression using 23 factorial design to evaluate the effect of formulation variables (Ac-di-sol concentration 5 or 10%, the ratio of soluble polymer 1:1 or 1:3 and binder type 6% w/w Avicel PH102 or 6% w/w carboxymethyl cellulose) on release characteristics. Results showed that lyophilized ODTs disintegrated within few seconds and had significantly faster dissolution rate (70-100 % in 5 minutes) compared to the commercial oral tablet (Cavinton®). This was achieved at high content of PEG 4000 or 2 HP-β-CD in presence of 10 % w/w Ac-Di-Sol and 6 % w/w Avicel PH102. The extent of per oral absorption of vinpocetine was determined in healthy human volunteers using randomized crossover design. The relative bioavailability of selected solid dispersion and inclusion complex formulations were found to be 171.98 % and 196.06 % respectively. The study indicated that complexation of vinpocetine with 2-HP-βCD or dispersion in PEG 4000 followed by lyophilization are two successful strategies for enhancing the bioavailability of the drug from ODTs

Technology transfer in developing countries

Technology has a great effect on productivity, wealth, health and life style of individuals and countries. Due to the rapid growth of technologies and poor infrastructure in developing countries they feel that they are far behind developed countries and Technology transfer has become a great issue of concern for researchers, companies and policy makers. However, the technology transfer is very challenge process that contains enormous barriers and constrains such as lack of infrastructure and educational development of the people. One of main challenges faced by Technology transfer is to have a clear process by which to identify the most suitable technology from out of several alternative technologies. This paper present and discusses technology, transfer process, channels, challenges and barriers

Freeze Dried Quetiapine-Nicotinamide Binary Solid Dispersions: A New Strategy for Improving Physicochemical Properties and Ex Vivo Diffusion

Improving the physicochemical properties and oral bioavailability of quetiapine fumarate (QF) enabling enhanced antipsychotic attributes are the main aims of this research. The freeze dried solid dispersion strategy was adopted using nicotinamide (NIC) as highly soluble coformer. The prepared dispersions were characterized using scanning electron microscopy (SEM) differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). Static disc intrinsic dissolution rate and ex vivo diffusion through intestinal tissues were conducted and compared to pure quetiapine fumarate. The results demonstrated a highly soluble coamorphous system formed between quetiapine fumarate and nicotinamide at 1 : 3 molar ratio through H-bonding interactions. The results showed >14-fold increase in solubility of QF from the prepared dispersions. Increased intrinsic dissolution rate (from 0.28 to 0.603 mg cm −2 min −1 ) and faster flux rate through duodenum (from 0.027 to 0.041 mg cm −2 h −1 ) and jejunum (0.027 to 0.036 mg cm −2 h −1 ) were obtained. The prepared coamorphous dispersion proved to be effective in improving the drug solubility and dissolution rate and ex vivo diffusion. Therefore, binary coamorphous dispersions could be a promising solution to modify the physicochemical properties, raise oral bioavailability, and change the biopharmaceutics classification (BCS) of some active pharmaceutical ingredients