〈476〉 Control of Organic Impurities in Drug Substances and Drug Products

2021 ◽  
Keyword(s):  
Drug Products ◽  
Drug Substances ◽  
Organic Impurities

Review on Pharmaceutical Co-Crystals and Design Strategies

2021 ◽  
pp. 175-180
Author(s):  
A.V.S. Ksheera Bhavani ◽  
A. Lakshmi Usha ◽  
Kayala Ashritha ◽  
Radha Rani E.
Keyword(s):  
Aqueous Solubility ◽  
Active Pharmaceutical Ingredient ◽  
Crystal Formation ◽  
Stoichiometric Ratio ◽  
Design Strategies ◽  
Great Opportunity ◽  
Drug Products ◽  
Drug Substances ◽  
Component Systems ◽  
Physical And Chemical

Poor aqueous solubility and low oral bioavailability of an active pharmaceutical ingredient are the major constraints during the development of new product. Various approaches have been used for enhancement of solubility of poorly aqueous soluble drugs, but success of these approaches depends on physical and chemical nature of the molecules being developed. Co-crystallization of drug substances offers a great opportunity for the development of new drug products with superior physicochemical such as melting point, tabletability, solubility, stability, bioavailability and permeability, while preserving the pharmacological properties of the active pharmaceutical ingredient. Co-crystals are multi component systems in which two components, an active pharmaceutical ingredient and a coformer are present in stoichiometric ratio and bonded together with non-covalent interactions in the crystal lattice. This review article presents a systematic overview of pharmaceutical co-crystals, differences between co-crystals with salts, solvates and hydrates are summarized along with the advantages of co-crystals with examples. The theoretical parameters underlying the selection of coformers and screening of co-crystals have been summarized and different methods of co-crystal formation and evaluation have been explained.

scholarly journals Artifact Peaks Due to Minor Decomposition of Sample Diluent DMSO in Head Space-GC Analysis: Mass Spectrometric Investigation Using Deuterated DMSO and Quadrupole Time-of-Flight Mass Detection

2021 ◽  
Author(s):  
Jinsheng Lin ◽  
Qiang Zhou ◽  
Jun Wang ◽  
Dandan Tang ◽  
Wenquan Zhu ◽  
...  
Keyword(s):  
Method Development ◽  
Formation Mechanisms ◽  
Mass Detection ◽  
Residual Solvents ◽  
Analytical Technique ◽  
Gc Analysis ◽  
Drug Products ◽  
Drug Substances ◽  
Head Space ◽  
Stress Study

<p><b>Rationale: </b>Head space gas chromatography (HS-GC) has become a widely used analytical technique for residual solvents determination in drug substances and drug products. During our method development of residual solvents by HS-GC for certain drug substances, four unknown peaks were observed when dimethyl sulfoxide (DMSO) was employed as sample diluent.</p><p><b>Methods:</b> Use of other sample diluents replacing DMSO did not show these unknown peaks in the HS-GC analysis. HS-GC-MS was then utilized to investigate these peaks. As part of the investigation, DMSO-<i>d<sub>6</sub></i> was used to trace the origins of these unknown peaks to DMSO. A stress study of methanethiol and formic acid was carried out to provide further evidence that <i>S</i>-methyl methanethioate was one of the unknown peaks observed during the original HS-GC analysis.<b></b></p><p><b>Results:</b> The four unknown peaks have been identified as methanethiol, dimethylsulfide, <i>S</i>-methyl methanethioate, and dimethyldisulfide, respectively, and it has been demonstrated that the four peaks are clearly related to DMSO through the use of its deuterated counterpart. Plausible formation mechanisms of these species are proposed.</p><p><b>Conclusions:</b> The occurrence of the peaks is due to minor degradation of DMSO, facilitated by certain drug substances as analytes of the analysis. These peaks are artifacts, rather than genuine impurities of the drug substances. These artifact peaks could widely occur in HS-GC analysis, when DMSO is used as sample diluent.</p>

scholarly journals Development of a Pediatric Relative Bioavailability/Bioequivalence Database and Identification of Putative Risk Factors Associated With Evaluation of Pediatric Oral Products

2021 ◽  
Vol 23 (3) ◽  
Author(s):  
Gopal Pawar ◽  
Fang Wu ◽  
Liang Zhao ◽  
Lanyan Fang ◽  
Gilbert J. Burckart ◽  
...  
Keyword(s):  
Risk Factors ◽  
Relative Bioavailability ◽  
Individual Variability ◽  
Cochrane Library ◽  
Factors Associated ◽  
Drug Products ◽  
Pharmaceutical Ingredients ◽  
Drug Substances ◽  
Age Related ◽  
Pediatric Populations

AbstractGenerally, bioequivalence (BE) studies of drug products for pediatric patients are conducted in adults due to ethical reasons. Given the lack of direct BE assessment in pediatric populations, the aim of this work is to develop a database of BE and relative bioavailability (relative BA) studies conducted in pediatric populations and to enable the identification of risk factors associated with certain drug substances or products that may lead to failed BE or different pharmacokinetic (PK) parameters in relative BA studies in pediatrics. A literature search from 1965 to 2020 was conducted in PubMed, Cochrane Library, and Google Scholar to identify BE studies conducted in pediatric populations and relative BA studies conducted in pediatric populations. Overall, 79 studies covering 37 active pharmaceutical ingredients (APIs) were included in the database: 4 bioequivalence studies with data that passed BE evaluations; 2 studies showed bioinequivalence results; 34 relative BA studies showing comparable PK parameters, and 39 relative BA studies showing differences in PK parameters between test and reference products. Based on the above studies, common putative risk factors associated with differences in relative bioavailability (DRBA) in pediatric populations include age-related absorption effects, high inter-individual variability, and poor study design. A database containing 79 clinical studies on BE or relative BA in pediatrics has been developed. Putative risk factors associated with DRBA in pediatric populations are summarized.

Accelerating pre-formulation investigations in early drug product lifecycle using predictive methodologies and computational algorithms

2021 ◽  
Author(s):  
Harsh S Shah ◽  
Kaushalendra Chaturvedi ◽  
Shanming Kuang ◽  
Jian Wang
Keyword(s):  
Case Studies ◽  
Drug Product ◽  
Analytical Techniques ◽  
Cost Effective ◽  
Product Lifecycle ◽  
Predictive Tools ◽  
Drug Products ◽  
Current Trends ◽  
Drug Substances ◽  
Early Drug

Precisely developed computational methodologies can allow the drug product lifecycle process to be time-efficient, cost-effective and reliable through a thorough fundamental understanding at the molecular level. Computational methodologies include computational simulations, virtual screening, mathematical modeling and predictive tools. In light of current trends and increased expectations of product discovery in early pharmaceutical development, we have discussed different case studies. These case studies clearly demonstrate the successful application of predictive tools alone or in combination with analytical techniques to predict the physicochemical properties of drug substances and drug products, thereby shortening research and development timelines. The overall goal of this report is to summarize unique predictive methodologies, which can assist pharmaceutical scientists in achieving time-sensitive research goals and avoiding associated risks that can potentially affect the drug product quality.

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