ABSTRACT
It is a challenging and important project to prolong the in vivo half life of protein and peptide drugs by physicochemical methods without new molecular entities generation. Protein crystallization provides a new strategy for improving the stability and in vivo delivery of these drugs. We show here that recombinant human interferon-alpha (rhIFN) can form spherical crystals. The physical and chemical features of the crystals were characterized, and drug dissolution was determined in vitro. The pharmacokinetics of crystallized interferon after sc injection in rabbit at 1.5 x 10(7) U x kg(-1) was compared to that of soluble form. The crystals were characterized as mono-dispersed spheres, with yield of > 80%, mean diameter size of about 16 microm and crystallinity of 23.2%. The in vitro dissolution behavior of crystallized rhIFN was featured as low initial burst release (21% within the first 2 h) and prolonged cumulative dissolution time up to 72 h without biological potency lost. After sc administration of soluble and crystallized interferon in rabbits, the peak time (T(max)) and half life (t1/2) were prolonged from (1.80 +/- 0.45) h and (1.35 +/- 0.35) h to (13.20 +/- 2.68) h and (10.68 +/- 1.97) h, respectively. The corresponding peak concentration decreased from (1 411.10 +/- 575.28) U x mL(-1) to (721.37 +/- 206.55) U x mL(-1). PK/PD analysis indicated that (96.87 +/- 20.30) % of relative bioavailability was obtained. The research results of this work will provide important academic value and application prospect for improving clinical therapeutic effect and development of biomacromolecules delivery system for protein and peptide drugs.
ABSTRACT
The pharmacodynamics of prostaglandin E1 (PGE1) administered by different routes to rats was investigated in this paper. The hypotensive effect of PGE1 was used as an index of drug efficacy, pharmacodynamic parameters such as time to reach peak effect (Tmax), maximal percentage of blood pressure decrease (Emax, %), duration of effect (Td), and the area determined after PGE1 given to rats intranasally, sublingually, intraperitoneally (ip),and intramuscularly (im), separately, and compared with those obtained from intravenous (iv) administration. Similar to iv route, the pharmacodynamic parameters of PGE1 from the other administration routes, Emax, Td and in particular AUC values were all increased with increasing doses, showing dose-efficacy relationship. Tmax was found to be approximately 3-4 min for nasal route, 3-8 min for im, 6-8 min for ip and 12-30 min for sublingual route, separately. Thus, the order of magnitude of absorption rate of the drug was as follows: nasal≈im＞ip＞sublingual. If the pharmacological bioavailability (PF) for each administration route was used as a tentative measure of drug absorption extent, the order of magnitude of absolute bioavailability appeared as follows: nasal＞im≈ip＞sublingual. Furthermore, the interindividual difference was found to be larger for im and ip route than that for nasal and sublingual route. These results indicate nasal and sublingual routes are two promising routes for the systemic delivery of PGE1 in clinical applications.
ABSTRACT
Aim Enteric microspheres were prepared to prevent the interaction of drug with gastric acid and to improve its bioavailability. Methods The enteric microspheres with a matrix structure were successfully produced using a spherical crystallization technique. Hydroxypropyl methylcellulose phthalate ( HP-55 ), an enteric material, was coprecipitated with the drug by salting-out effect during the preparation process. A mixture of water and ethanol was chosen as a good solvent and dichloromethane was used as a the first time to prepare microspheres by making the water-soluble drug and water-insoluble excipient coprecipitated. In vivo test demonstrated that the drug absorption from the enteric oleanolic acid dihemiphthalate sodium (OADHPS) microspheres was significantly prolonged compared to that with OADHPS powder after a lag-time. Furthermore, the drug bioavailability was 181.6% greater than that with the OADHPS powder. Conclusion The microspheres of water soluble drug could be prepared by using water phase replacing organic phase as poor solvent which decrease the quantity of organic solvent and benefit the environment prevention.
ABSTRACT
Objective To obtain the same release rate of four index components with significant difference of physicochemical characters,puerarin,baicalin berberine and glycyrrhizin in Gegen Qinlian Pellets.Methods Studies on improving the release rate of less soluble components in Gegen Qinlian Pellets were carried out and the parameters were optimized.The release profiles were analyzed by simulating factor(f_2).Results The f_2 values for baicalin,berberine and glycyrrhizin vs puerarin were 52.27,56.13,and 75.1,respectively.Conclusion The result shows that the same release rate of four index components in Gegen Qinlian Pellets is obtained.
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Objective To prepare Gegen Qinlian Pellets with higher yield of drug loading and being good for industrial production.Methods The Gegen Qinlian Pellets were prepared by extrusion-spheronization.The effects of four key parameters on spheronization process were the proportion of bond,extrusion speed,spheronisation speed,and spheronisation time,which were investigated to obtain optimal formulation.Results Gegen Qinlian Pellets presented perfect sphericity and narrow diameter distribution.Drug loading in the pellets could be up to 70% and yelid over 90%.Conclusion The Gegen Qinlian Pellets are successfully prepared by extrusion-spheronization.It presents a method for industria-lized production of Chinese materia medica.
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AIM: To study a method for the determination of Zedoary turmeric oil microsphere (ZTO-MS). METHODS: ZTO-MS was extracted supersonically by solvent and then colored by sulfuric acid-vanillin reagent. The absorbance was measured by visible-spectrophotometry at 508nm. At the same time, ZTO-MS also could be determined by HPLC. RESULTS: The content of Zedoary turmeric oil was above 60% and the contents of Curdione、Curcuma、Germacrone were 6.88%,0.95%,5.0%, respectively, in ZTO-MS. CONCLUSION: Two methods for the determination of ZTO-MS are accurate, reliable; the method of visible-spectrophotometry is convenient and appropriate for determination for content of oil in ZTO-MS, while the method of HPLC gains the advantage for qualitative and quantitative analysis of components in ZTO-MS.
ABSTRACT
Objective: To enhance the dissolution rate in vitro and bioavailability in vivo of the active components of extraction of Radix Arnebiae seu Lithospermi. Methods: Solid dispersion of extract of Radix Arnebiae seu Lithospermi were prepared with solid dispersion technology, X ray diffraction and stability experiments were also carried out. Results: The dissolution rates in vitro of the active components of extraction of Radix Arnebiae seu Lithospermi solid dispersion were obviously raised and stable, and the solid dispersion was not easy to age. Conclusion: The dissolution rate in vitro of the active components in Radix Arnebiae seu Lithospermi can be inproved greatly by the solid dispersion using PVP and HPMC as a carrier.