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

APPLICATION OF TWO ADVANCED DERIVATIVE SPECTROPHOTOMETRIC METHODS FOR SIMULTANEOUS ESTIMATION OF SALBUTAMOL SULPHATE, AMBROXOL HYDROCHLORIDE AND THEOPHYLLINE IN PURE AND COMMERCIAL FORMULATIONS

Objective: Two advanced spectrophotometric methods have been proposed for the simultaneous determination of Salbutamol sulphate, Ambroxol hydrochloride and Theophylline in pure and pharmaceutical formulations. The proposed methods exclude the hectic steps of time-consuming sample preparations or purification or separation steps. There is no any spectrophotometric method has been avail for simultaneous estimation of the ternary mixture containing Salbutamol sulphate, Ambroxol hydrochloride and Theophylline. Methods: The methods are derivative ratio spectra zero-crossing method and double divisor ratio spectra derivative method respectively. Both the methods are found to be rapid, accurate, precise, reliable and economical as well. The developed methods show best results in terms of linearity, accuracy, precision, limit of detection and limit of quantification for standard laboratory mixtures of pure drugs and marketed formulations. Results: The range for Salbutamol sulphate, Ambroxol hydrochloride and Theophyllineare found to be 1-35 µg ml-1, 5-35 µg ml-1and 6-60 µg ml-1 respectively. For the derivative ratio spectra zero-crossing method, the values of the limit of detection are found to be 0.3161 µg ml-1, 0.2212 µg ml-1 and 0.2910 µg ml-1 and the values limit of quantification are found to be 0.9571 µg ml-1, 0.7412 µg ml-1 and 0.9671 µg ml-1 for Salbutamol sulphate, Ambroxol hydrochloride and Theophylline respectively. For double divisor ratio spectra derivative method, limit of detection values is found to be 0.3251 µg ml-1, 0.2591 µg ml-1 and 0.2640 µg ml-1 and the limit of quantification values are found to be 0.9870 µg ml-1, 0.8650 µg ml-1 and 0.8812 µg ml-1 for Salbutamol sulphate, Ambroxol hydrochloride and Theophylline respectively. Conclusion: The common excipients and additives did not interfere in the determinations of any of the drugs while being analysed for commercial formulations. These two spectrophotometric methods, which determine SS, AH, and THE simultaneously, are simple, specific, accurate, precise, rapidly, and economically, indicating that they can be used routinely in pharmaceutical analysis. As a result, derivative spectrophotometry may be used effectively for the simultaneous determination of SS, AH and THE in the combined dosage forms without any prior separation of individual drugs

A Novel Itraconazole Bioadhesive Film for Vaginal Delivery: Design, Optimization, and Physicodynamic Characterization

The purpose of this work was to design and optimize a novel vaginal drug delivery system for more effective treatment against vaginal candidiasis. Itraconazole was formulated in bioadhesive film formulations that could be retained in the vagina for prolonged intervals. The polymeric films were prepared by solvent evaporation and optimized for various physicodynamic and aesthetic properties. In addition, percentage drug retained on vaginal mucosa was evaluated using a simulated dynamic vaginal system as function of time. A polymeric film containing 100 mg itraconazole per unit (2.5 cm × 2.5 cm) have been developed using generally regarded as safe listed excipients. The pH of vaginal film was found to be slightly acidic (4.90 ± 0.04) in simulated vaginal fluid and alkaline (7.04 ± 0.07) in water. The little moisture content (7.66 ± 0.51% w/w) was present in the film, which helps them to remain stable and kept them from being completely dry and brittle. The mechanical properties, tensile strength, and percentage elongation at break (9.64 N/mm2 and 67.56% for ITRF65) reveal that the formulations were found to be soft and tough. The films (ITRF65) contained solid dispersion of itraconazole (2.5)/hydroxypropyl cellulose (1)/polyethylene glycol 400 (0.5), which was found to be the optimal composition for a novel bioadhesive vaginal formulation, as they showed good peelability, relatively good swelling index, and moderate tensile strength and retained vaginal mucosa up to 8 h. Also, the film did not markedly affect normal vaginal flora (lactobacillus) and was noncytotoxic as indicated by the negligible decrease in cell viability

Effect of hydrophilic swellable polymers on dissolution enhancement of carbamazepine solid dispersions studied using response surface methodology

The objective of this work was to study dissolution enhancement efficiency and solid dispersion formation ability of hydrophilic swellable polymers such as sodium carboxymethyl cellulose (Na-CMC), sodium starch glycolate (SSG), pregelatinized starch (PGS), and hydroxypropylmethyl cellulose (HPMC) with carbamazepine using 32 full factorial design for each of the polymers. Solid dispersions of carbamazepine were prepared using solvent evaporation method with around 70% solvent recovery. The independent variables were the amount of polymer and organic solvent. The dependent variables assessed were percentage drug dissolved at various time points and dispersion efficiency (ie, in terms of particle size of solid dispersion). Solid dispersions were evaluated for percentage drug dissolved, wettability, differential scanning calorimetry, scanning electron microscopy, and angle of repose. Multiple linear regression of results obtained led to equations, which generated contour plots to relate the dependent variables. Similarity factor and mean dissolution time were used to compare dissolution patterns obtained in distilled water and simulated gastric fluid United States Pharmacopeia (USP) XXVI of pH 1.2. Maximum drug dissolution was obtained with polymer order Na-CMC>SSG>PGS>HPMC. Particle size of drug was reduced ≈ 10–15, 3–5, 5–7, and 10–25 times in Na-CMC, SSG, PGS, and HPMC solid dispersions, respectively; whereas wettability of solid dispersions was found in the order of Na-CMC>HPMC>PGS>SSG. Angle of repose was found to be in the range of 29° to 35° for all solid dispersions, which shows good flowability characteristics. HPMC showed increase in drug dissolution up to an optimized level; however, furthers increase in its concentration decreased drug dissolution

Formulation and Evaluation of Taste Masked Oral Reconstitutable Suspension of Primaquine Phosphate

The purpose of this research was to mask the intensely bitter taste of primaquine phosphate (PRM) and to formulate suspension powder (cachets) of the taste masked drug. Taste masking was done using beta-cyclodextrin. To characterize and formulate taste masked cachets of PRM, the 1:25 M physical mixture was selected based on bitterness score. Phase solubility studies, fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray powder diffraction (XRPD) were performed to identify the physicochemical interaction between drug and carrier, hence its effect on dissolution. Cachets were evaluated for angle of repose, sedimentation characterization and pH. In vitro drug release studies for physical mixture and kneaded system were performed at pH, 1.2 and 6.8. Bitterness score was evaluated using gustatory sensation test. Phase solubility studies showed weak interaction between PRM and CD. The FTIR, DSC and XRPD studies indicated inclusion complexation in physical mixture and kneaded system. In addition, kneaded system and physical mixture exhibited better drug release at pH 1.2 and negligible effect at pH 6.8. Cachets prepared using physical mixture, (DS24), showed complete bitter taste masking and easy redispersibility. Taste evaluation of cachets in human volunteers rated tasteless with a score of 0 to DS24 and 3 to DS25. Thus, results conclusively demonstrated successful taste masking and formulation of cachets with taste masked drug