A practical guide to pharmaceutical polymorph screening & selection

Prevalence and importance of polymorphism occurring in pharmaceutical compounds are well recognized.It is of great importance to prepare and select the right form from the beginning during drug discovery and development.This review introduces the basic concepts of“What is polymorphism?”,addresses a fundamental question of“Why do polymorphs form?”,and provides practical guidelines of“How to prepare polymorphs?”“How to evaluate the relative thermodynamic stability between polymorphs?”,and“How to analyze polymorphs?”.Moreover,case studies of pharmaceutically important polymorphs are provided.

Screening, Characterization and Evaluation of Mangiferin Polymorphs

Mangiferin is a compound with many pharmacological activities and exists in many natural products.Anhydrous and hydrate of mangiferin have been reported separately in two literatures,but the polymorphism of this compound has not been realized until this paper.In this study,polymorph screening of mangiferin has been carried out and five forms have been obtained including three new forms never reported.Several solid state characterization methods,such as powder X-ray diffraction,differential scanning calorimetry and thermogravimetry,are used to identify and characterize all of mangiferin forms.The comparison of the crystallographic data and hirshfeld surface analysis were first reported for mangiferin anhydrous and hydrate.Furthermore,the studies on stability,transformation and solubility have been undertaken,the results prompt that form V can be used as the dominant polymorph for the development of innovative pharmaceuticals.

Sequence-related amplified polymorphism primer screening on Chinese fir(Cunninghamia lanceolata(Lamb.) Hook)

Chinese fir（Cunninghamia lanceolata（Lamb.）Hook） is one of the most important coniferous tree species used for timber production in China. Here, we conducted a sequence-related amplified polymorphism（SRAP） primer screening assay with a total of 594 primer combinations,using 22 forward and 27 reverse primers on four representative Chinese fir genotypes. The obtained results indicated that Chinese fir genomic DNA has a notable amplification bias on the employed forward or reverse primer nucleotides（30selection bases）. Out of the tested primer sets, 35 primer combinations with clearly distinguished bands, stable amplification, and rich polymorphism were selected and identified as optimal primer sets. These optimal primer pairs gave a total of 379 scorable bands,including 265 polymorphic bands, with an average of 10.8bands and 7.6 polymorphic bands per primer combination.The produced band number for each optimal primer set ranged from 7 to 14 with a percentage of polymorphic bands spanning from 33.3 to 100.0 %. These primer combinations could facilitate the next SRAP analysis assays in Chinese fir.

Genetic Diversity Analysis of Rice Germplasm in Tripura State of Northeast India Using Drought and Blast Linked Markers

We genotyped 74 rice germplasms including Tripura＇s local landraces, improved varieties, cultivars and breeding lines and other rice varieties using molecular markers for genetic diversity, drought QTLs, and blast resistance genes. The number of alleles per locus ranged from 2 to 5 with an average of 2.9. The polymorphic information content value per locus ranged from 0.059（RM537） to 0.755（RM252） with an average of 0.475. Cluster analysis based on 30 simple sequence repeat markers revealed 5 clusters and also indicated the presence of variability within the rice accessions. The drought QTL q DTY2.1 was found in 56.0% of germplasms and q DTY1.1 was detected in only 6.8% of the germplasms. Out of seven rice blast resistance genes screened, only two rice varieties, RCPL-1-82 and Buh Vubuk（Lubuk）, were positive for four blast resistance genes while only Releng possessed two blast resistance genes. Among 74 rice germplasms, only three accessions, Releng, RCPL1-82 and Buh Vubuk（Lubuk）, possessed both drought-related QTLs and blast resistance genes. Overall, the 74 indigenous rice genotypes showed low level of genetic diversity, which is in contrast to high level of genetic diversity among rice varieties in northeast India, where highlights the good farming practice, conservation of germplasms and the limitation of molecular markers employed in this study. The presence of both drought related QTLs and blast resistance genes in some of the germplasms can be useful in future breeding programmes.