Fast Dissolving Sublingual Films of Ondansetron Hydrochloride: Effect of Additives on in vitro Drug Release and Mucosal Permeation

Ondansetron hydrochloride, a 5 HT3 antagonist is a powerful antiemetic drug which has oral bioavailability of 60% due to hepatic first pass metabolism and has a short half-life of 5 h. To overcome the above draw back, the present study was carried out to formulate and evaluate fast dissolving films of ondansetron hydrochloride for sublingual administration. The films were prepared from polymers such as polyvinylalcohol, polyvinyl pyrrolidone, Carbopol 934P in different ratios by solvent casting method. Propylene glycol or PEG 400 as plasticizers and mannitol or sodium saccharin as sweeteners were also included. The IR spectral studies showed no interaction between drug and polymer or with other additives. Satisfactory results were obtained when subjected to physico-chemical tests such as uniformity of weight, thickness, surface pH, folding endurance, uniformity of drug content, swelling index, bioadhesive strength, and tensile strength. Films were also subjected to in vitro drug release studies by using USP dissolution apparatus. Ex vivo drug permeation studies were carried out using porcine membrane model. In vitro release studies indicated 81–96% release within 7 min and 66–80% within 7 min during ex vivo studies. Drug permeation of 66–77% was observed through porcine mucosa within 40 min. Higher percentage of drug release was observed from films containing the sweeteners. The stability studies conducted for a period of 8 weeks showed no appreciable change in drug content, surface pH, and in vitro drug release

Priprava i evaluacija mukoadhezivnih filmova glipizida

Glipizide is mainly absorbed in the proximal areas of the gastrointestinal tract. The purpose of this study was formulation and evaluation of mucoadhesive films to prolong the stay of drug in its absorption area. Glipizide was formulated in a mucoadhesive film that could be retained in the stomach for prolonged time intervals. Polymeric films were designed with various compositions of hydroxypropyl cellulose and polyethylene glycol 400 (PEG 400). Properties of the mucoadhesive film such as tensile strength, percentage elongation, swelling index, moisture content, pH and viscosity of polymeric dispersion, film thickness, drug concentration, uniformity and mucoadhesion in a simulated gastric environment were evaluated. In addition, percentage drug retained in stomach mucosa was estimated using a simulated dynamic stomach system as a function of time. Increase in hydroxypropyl cellulose concentration resulted in a higher tensile strength and elongation at break, while increase in concentration of PEG 400 was reflected in a decrease of tensile strength and increase of elongation at break. Glipizide/hydroxypropyl cellulose/PEG 400 (2.5:1:0.5) (GF5) was found to be the optimal composition for a novel mucoadhesive stomach formulation that showed good peelability, relatively high swelling index, moderate tensile strength, and stayed on rat stomach mucosa up to 8 h. In vivo testing of the mucoadhesive films with glipizide demonstrated a potential hypoglycemic effect.Glipizid se pretežno apsorbira u proksimalnom dijelu gastrointestinalnog trakta. Cilj rada je priprava i evaluacija mukoadhezivnih filmova s kojima bi se produljilo zadržavanje lijeka u predjelu apsorpcije. Pripravljeni su mukoadhezivni filmovi glipizida koji se produljeno zadržavaju u želucu. Polimerni filmovi sadržavali su različite količine hidroksipropil celuloze i polietilen glikola 400 (PEG 400). Evaluirana su sljedeća svojstva mukoadhezivnih filmova: čvrstoća, postotak elongacije, indeks bubrenja, sadržaj vlage, pH i viskoznost polimerne disperzije, debljina filma, koncentracija lijeka, jednolikost i mukoadhezivnost u simuliranom želučanom soku. Na dinamičkom modelu želuca određivan je i postotak lijeka koji se zadržava u sluznici želuca u ovisnosti o vremenu. Povećanjem koncentracije hidroksipropil celuloze povećavaju se čvrstoća i elongacija, dok se povećanje koncentracije PEG 400 reflektira na smanjenje čvrstoće i povećanje elongacije kod loma. Omjer glipizid/hidroksipropil celuloza/PEG 400 (2,5:1:0,5) (GF5) bio je optimalan za pripravu mukoadhezivnih formulacija, s dobrom kalavošću, relativno visokim indeksom bubrenja, umjerenom čvrstoćom te zadržavanjem u sluznici želuca štakora do 8 h. U in vivo testiranjima mukoadhesivni filmovi s glipizidom pokazali su potencijalni hipoglikemijski učinak

Dizajniranje i optimizacija mikrokapsula artemetera za maskiranje gorkog okusa

The objective of the present investigation was to reduce the bitterness of artemether (ARM). Microparticles were prepared by the coacervation method using Eudragit E 100 (EE) as polymer and sodium hydroxide solution as nonsolvent for the polymer. A 32 full factorial design was used for optimization wherein the amount of drug (A) and polymer (B) were selected as independent variables and the bitterness score, particle size and drug release at pH, 1.2 and 6.8 were selected as dependent variables. Optimization was carried out using the desirability function. The optimized microparticles batch was characterized by FT-IR and DSC. Multiple linear regression analysis revealed that reduced bitterness of ARM can be obtained by controlling the drug release of microparticles at pH 6.8 and increasing the amount of EE. The increase in the amount of polymer leads to reduction in drug release from microparticles at pH > 5 due to its insolubility and thus reduces bitterness. However, the increase in the amount of polymer results in improved dissolution, suggesting improved availability of ARM in stomach. Optimized microparticles prepared using 0.04 g of ARM and 15 mL of 1% m/V solution of EE showed complete bitter taste masking with improved drug release at pH 1.2.Cilja ovog rada je bio maskirati gorki okus artemetera (ARM) mikrokapsuliranjem. Mikročestice su pripravljene metodom koacervacije pomoću Eudragita E 100 (EE) kao polimerne komponente i natrijevog hidroksida u kojem se polimer ne otapa. 32 faktorijalni dizajn upotrebljen je za optimizaciju. Količine ljekovite tvari (A) i polimera (B) izabrane su kao nezavisne varijable, a intenzitet gorkog okusa, veličina čestica i oslobađanje ljekovite tvari pri pH 1,2 i 6,8 izabrane su kao zavisne varijable. Optimizirane mikročestice karakterizirane su pomoću FT-IR i DSC. Multipla linearna regresijska analiza otkrila je da se smanjenje gorčine artemetera može postići kontroliranjem oslobađanja ljekovite tvari pri pH 6,8 i povećanjem količine EE. Povećanje količine polimera dovodi do smanjenja oslobađanja ljekovite tvari pri pH > 5 pa se smanjuje i gorčina. Međutim, povećanje količine polimera povećava topljivost ljekovite tvari, a time potencijalno i njenu raspoložljivost u želucu. U optimiziranim mikročesticama pripravljenim pomoću 0,04 g ARM i 15 mL 1% m/v otopine EE potpuno se maskirao gorki okus, a oslobađanje ljekovite tvari pri pH 1,2 bilo je poboljšano

Clinical Characteristics, Racial Inequities, and Outcomes in Patients with Breast Cancer and COVID-19: A COVID-19 and Cancer Consortium (CCC19) Cohort Study

BACKGROUND: Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations. METHODS: This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity. RESULTS: 1383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32-1.67]); Black patients (aOR 1.74; 95 CI 1.24-2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70-6.79) and Other (aOR 2.97; 95 CI 1.71-5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83-12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63-3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20-2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66-3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89-22.6]). Hispanic ethnicity, timing, and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status. CONCLUSIONS: Using one of the largest registries on cancer and COVID-19, we identified patient and BC-related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to non-Hispanic White patients. FUNDING: This study was partly supported by National Cancer Institute grant number P30 CA068485 to Tianyi Sun, Sanjay Mishra, Benjamin French, Jeremy L Warner; P30-CA046592 to Christopher R Friese; P30 CA023100 for Rana R McKay; P30-CA054174 for Pankil K Shah and Dimpy P Shah; KL2 TR002646 for Pankil Shah and the American Cancer Society and Hope Foundation for Cancer Research (MRSG-16-152-01-CCE) and P30-CA054174 for Dimpy P Shah. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH). The funding sources had no role in the writing of the manuscript or the decision to submit it for publication. CLINICAL TRIAL NUMBER: CCC19 registry is registered on ClinicalTrials.gov, NCT04354701

Timing and Outcomes of Hip Fracture Surgery During the COVID-19 Pandemic

Introduction: The effects of delayed surgical repair for traumatic hip fractures have been widely discussed in the literature, and there exists a strong association between surgical timing and patient outcomes. The COVID-19 pandemic placed a significant burden on health care systems throughout the world, with hospitals reallocating both human and physical resources to care for the critically ill. The purpose of this study is to investigate if the strain placed on hospital systems by COVID-19 and the changes to hospital operational models negatively impacted time to surgery, as well as morbidity and mortality rates of hip fractures. Methods: A retrospective chart review was performed on 416 patients 18 years or older who were treated for traumatic hip fractures between January 2019 and November 2020 at a single academic Level 1 trauma center. Pre-operative and post-operative data were collected for each patient. The incidence of mortality and complications were captured. Statistical analysis performed were Independent T Test, Mann Whitney U Test, Chi Squared Test, Linear and Logistic Regressions to compare outcomes of patients. Results: Two-hundred sixty-three patients were treated pre-pandemic (control; January 2019-February 2020) and 153 were treated during the pandemic (experimental; March 2020-November 2020). There were no significant differences in median time to surgery between control and experimental (22 versus 23 hours) groups, as well as no difference in readmission rates (23.2% versus 17.0%; p=0.134), overall reoperation rates (6.1% versus 2.0%; p=0.052), and 30- (7.2% versus 3.3%, p=0.095) and 90-day (1.9% versus 3.9%; p=0.22) mortality rates. Conclusion: The established pre-pandemic practices for the throughput of hip fractures mitigated any negative impacts to surgical timing or complications during the pandemic. Time to surgery for traumatic hip fractures remains a challenge and often requires multidisciplinary care. As COVID-19 continues to impact workflow within hospitals, clinicians should strive to balance system-wide changes while ensuring timely intervention for hip fractures to optimize outcomes