ABSTRACT
The objective of this study was to develop solid solution (SSL) using hot-melt extrusion as a continuous manufacturing method. Powder blends of artesunate (ARS) a water insoluble drug with either Soluplus (SOL) or Kollidon VA64 (VA64) and additives in the form of surfactants or plasticizers were extruded to manufacture extrudes. The incorporation of surfactant or plasticizers facilitates smooth extrusion processing of the drug-excipient blend which directly reduced the residence time to form extrudes and works as parameter to control flow of the drug-excipients melt inside the extruder barrel. Differential scanning calorimetry (DSC) and X-ray diffraction (TXRD) analysis revealed the existence of the drug within the extrudes in amorphous state. Scanning electron microscopy (SEM), Raman spectroscopy (RS), Raman imaging (RI) and Atomic force microscopy (AFM) analytical characterization were carry out on the SSL formulations showed a homogeneous drug distribution within the extrudes. (2)D NMR and (1)H NMR studies were undertaken to reveal the possible drug-excipient interactions. The SSL produced via continuous HME processing showed significantly faster release of ARS compared to the pure drug substance. It is observed that F1 SSL (soluplus based) have 66.44 times higher AUC(0-72) and 16.60 times higher Cmax than pure ARS. Also K1 SSL (Kollidon VA64 based) have 62.20 times higher AUC(0-72) and 13.40 times higher Cmax than pure ARS.
Subject(s)
Antimalarials/administration & dosage , Artemisinins/administration & dosage , Excipients/chemistry , Polymers/chemistry , Animals , Antimalarials/chemistry , Antimalarials/pharmacokinetics , Area Under Curve , Artemisinins/chemistry , Artemisinins/pharmacokinetics , Artesunate , Calorimetry, Differential Scanning , Chemistry, Pharmaceutical/methods , Drug Liberation , Male , Plasticizers/chemistry , Polyethylene Glycols , Polyvinyls , Pyrrolidines/chemistry , Rats , Rats, Wistar , Solubility , Surface-Active Agents/chemistry , Vinyl Compounds/chemistry , X-Ray DiffractionABSTRACT
OBJECTIVE: To determine antimutagenic activity of Cassia auriculata Linn. on chromosomal damage induced by cyclophosphamide (CP). MATERIAL AND METHODS: In the present investigation, four groups of six Swiss albino mice in each group were used. Excepting for the first group all the remaining groups were treated with CP (50 mg/kg). Mice of third and fourth group were treated with ethyl acetate extract of C. auriculata Linn. at 100 mg/kg and 200 mg/kg with CP. Metaphase of bone marrow cells of all animals were analyzed for qualitative and quantitative chromosomal aberrations. Break, fragment, deletion, Polyploidy, pulverized, ring and total aberration were observed. RESULTS: Flavonoids rich extracts of root of C. auriculata Linn. provided significant protection (P < 0.05) against CP induced chromosomal aberration. Total chromosomal aberration was found to be 12.16 and 7.33% in 100 and 200 mg/kg of extract treated animals respectively. CONCLUSION: From the present study it can was observed that ethyl acetate extract of C. auriculata Linn possess significant anti-mutagenic potential against CP induced chromosomal aberration.
