ABSTRACT
Cryptotanshinone, tanshinone I and tanshinone IIA are three major components in the extract of Salvia miltiorrhiza with pharmacological significance. However, their effective utilization is limited due to poor water solubility and bioavailability. Solid dispersion (SD) of the extract of Salvia miltiorrhiza was prepared to enhance solubility and dissolution of the three major components. Various carriers were screened for SD preparation by conventional solvent method. Dissolution of the components from selected SD systems was compared with commercial tablets of the extract from Salvia miltiorrhiza. The solubility of three components viz., cryptotanshinone, tanshinone I and tanshinone IIA, after forming SD with either of povidone K-30 (PVP K-30) or poloxamer 407, exhibited enhanced solubility in pH 6.8 buffer. Dissolution test revealed that the amount of three components released was higher from SD tablets as compared to the commercial tablets. Pharmacokinetic profile was evaluated using cryptotanshinone as a representative compound. AUC of cryptotanshinone was significantly increased when administered as a solid dispersion.
Subject(s)
Abietanes/chemistry , Phenanthrenes/chemistry , Plant Extracts/chemistry , Salvia miltiorrhiza/chemistry , Abietanes/isolation & purification , Animals , Area Under Curve , Drug Carriers/chemistry , Hydrogen-Ion Concentration , Male , Phenanthrenes/isolation & purification , Phenanthrenes/pharmacokinetics , Plant Extracts/administration & dosage , Plant Extracts/pharmacokinetics , Poloxamer/chemistry , Povidone/chemistry , Rats , Rats, Sprague-Dawley , Solubility , Solvents/chemistry , TabletsABSTRACT
This study aimed to develop a stable solid dispersion of Coenzyme Q(10) (CoQ(10)) with high aqueous solubility and dissolution rate. Among various carriers screened, poloxamer 407 was most effective to form a superior solid dispersion of CoQ(10) having significantly enhanced solubility. Particularly, solid dispersion of CoQ(10) with poloxamer 407 in the weight ratio of 1:5 prepared by melting method enhanced the solubility of CoQ(10) to the greatest extent. However, it exhibited poor stability and hence Aerosil 200 (colloidal silicon dioxide) was incorporated into the solid dispersion as an adsorbent to inhibit the recrystallization process. The solid dispersion of CoQ(10), poloxamer 407 and Aerosil 200 in the weight ratio of 1:5:6 exhibited improved stability with no significant change in solubility during the 1-month stability test. Moreover, the solid dispersion formulation containing Aerosil 200 significantly enhanced the extent of drug release (approx. 75% release) as well as the dissolution rate of CoQ(10). In conclusion, the present study has developed the stable solid dispersion formulation of CoQ(10) with poloxamer 407 and Aerosil 200 for the enhanced solubility and dissolution of CoQ(10), which could also offer some additional advantages including ease of preparation, good flowability and cost-effectiveness.
Subject(s)
Chemistry, Pharmaceutical/methods , Ubiquinone/analogs & derivatives , Drug Carriers/chemical synthesis , Drug Carriers/chemistry , Drug Carriers/metabolism , Enzyme Stability , Microscopy, Electron, Scanning , Poloxamer/chemistry , Poloxamer/metabolism , Solubility , Ubiquinone/chemical synthesis , Ubiquinone/chemistry , Ubiquinone/metabolism , Ubiquinone/ultrastructureABSTRACT
Coenzyme Q(10) (CoQ(10)) was formulated into self-nanoemulsifying drug delivery systems (SNEDDS) to overcome low bioavailability attributed to hydrophobic nature of the drug. Screening of oil phase, surfactants and co-surfactants were performed to select Witepsol H35, Solutol HS15 and Lauroglycol FCC, respectively. Ternary phase diagrams were drawn to identify nanoemulsifying region followed by optimization of SNEDDS formulation. The optimized formulation, CoQ(10), Witepsol H35, Solutol HS15 and Lauroglycol FCC in the weight ratio of 1:0.7:4:2, respectively, emulsified readily at 37 degrees C with mean emulsion droplet size of 32.4 nm. The stability test of the optimized formulation in pH 1.2 and 6.8 buffers confirmed no pH effect on emulsion droplet size. In vitro dissolution (emulsification) test and in vivo animal study of the formulation elucidated the complete emulsification of drug and improved oral bioavailability of poorly soluble CoQ(10).
Subject(s)
Drug Delivery Systems/methods , Emulsifying Agents/administration & dosage , Nanotechnology , Triglycerides/administration & dosage , Ubiquinone/analogs & derivatives , Animals , Drug Evaluation, Preclinical/methods , Emulsifying Agents/blood , Emulsifying Agents/chemical synthesis , Male , Nanotechnology/methods , Rats , Rats, Sprague-Dawley , Triglycerides/blood , Triglycerides/chemical synthesis , Ubiquinone/administration & dosage , Ubiquinone/blood , Ubiquinone/chemical synthesisABSTRACT
The aim of this study was to develop floating microspheres with practical applications to fish farming. Each microsphere with a central hollow cavity was prepared using a solvent diffusion and evaporation method with Eudragit E100. Various manufacturing parameters were investigated by single factor method. The macrolide antibiotic josamycin was selected as a model drug. The loading efficiency of the drug in the microspheres was 64.7%. In the release study, virtually none of the drug was released into the fresh water whereas the entire drug was released from the josamycin-loaded microspheres into the simulated gastric fluid of rainbow trout (pH 2.7). The buoyancy was excellent with approximately 90% of the microspheres still floating after 24h.
