A pH-independent instantaneous release of flurbiprofen: a study of the preparation of complexes, their characterization and in vitro/in vivo evaluation.

In this study, furbiprofen/hydroxypropyl-ß-cyclodextrin (HPßCD) inclusion complexes were prepared to improve the drug dissolution and facilitate its application in hydrophilic gels. Inclusion complexes were prepared using a supercritical fluid processing and a conventional optimized co-lypholization method was employed as a reference. The entrapment efficacy and drug loading of both methods were investigated. Evaluation of drug dissolution enhancement was conducted in deionized water as well as buffer solutions of different pH. Carbopol 940 gels of both flurbiprofen and flurbiprofen/HPßCD inclusion complexes, with or without penetration enhancers, were prepared and percutaneous permeation studies were performed using rat abdominal skin samples. Formation of flurbiprofen/HPßCD inclusion complexes was confirmed by Fourier transform-infrared spectroscopy, differential scanning calorimetry, X-ray diffraction and scanning electron microscopy. The results obtained showed that SCF processing produced a higher EE (81.91 ± 1.54%) and DL (6.96 ± 0.17%) compared with OCL with values of 69.11 ± 2.23% and 4.00 ± 1.01%, respectively. A marked instantaneous release of flurbiprofen/HPßCD inclusion complexes prepared by SCF processing (103.04 ± 2.66% cumulative release within 5 min, a 10-fold increase in comparison with flurbiprofen alone) was observed. In addition, this improvement in dissolution was shown to be pH-independent (the percentage cumulative release at pH 1.2, 4.5, 6.8 and 7.4 at 5 min was 95.19 ± 1.71, 101.75 ± 1.44, 105.37 ± 4.58 and 96.84 ± 0.56, respectively). Percutaneous permeability of flurbiprofen-in-HPßCD-in-gels could be significantly accelerated by turpentine oil and was related to the water content in the system. An in vivo pharmacokinetic study showed a 2-fold increase in Cmax and a shortened Tmax as well as a comparable relative bioavailability when compared with the commercial flurbiprofen Cataplasms (Zepolas®). With their superior dissolution, these flurbiprofen/HPßCD inclusion complexes prepared by SCF processing could provide improved applications for flurbiprofen.

Manufacture and characteristics of asymmetric membrane capsule shells with a novel wet phase inversion method.

In order to overcome the difficulty in stripping and to improve the automaticity and efficiency, a novel method was developed to prepare asymmetric membrane capsule shells (AM-CSs). Soluble mold pins were used to replace conventional insoluble mold pins, and simplified process was designed. Investigated by scanning electron microscopy and dye test, the homemade AM-CSs had typical asymmetric structure, in situ pore formation ability and high water influx. The in vitro dissolution properties of AM-CSs and homogeneous membrane capsule shells (HM-CSs) were compared. The release behavior of Metoprolol Tartrate and Nimodipine from the AM-CSs was mainly dominated by osmosis, while no drug could release from HM-CSs. The novel wet phase inversion method had significant advantages as well as potential value to be used in pharmaceutical research and application.

In vitro and in vivo evaluation of gliclazide push-pull osmotic pump coated with aqueous colloidal polymer dispersions.

The objective of present work was to design and evaluate gliclazide push-pull osmotic pump (PPOP) coated with aqueous colloidal polymer dispersions-Eudragit(®) RL 30D and Eudragit(®) RS 30D. The influence of diacetin, diethyl phthalate (DEP), dibutyl sebacate (DBS) and triethyl citrate (TEC) on the free Eudragit(®) RL 30D and Eudragit(®) RS 30D films as plasticizers on drug release were studied. Among these four plasticizers, diacetin offered the smoothest surface of the cast films, and it displayed greatest water vapor transmission coefficient. Free RL and RS films with diacetin also exhibited greatest erosion compared with the other three plasticizers. On the other hand, TEC, DEP and DBS showed greater water absorption. When compared with CA-coated gliclazide PPOP, Eudragit-coated ones showed a f(2) factor of 71.7, indicating the similarity between the release profile of the two formulations. The prepared Eudragit-coated gliclazide PPOP showed typical Zero-order release characteristics, with R being 0.9953. In the in vivo evaluation, the mean relative oral bioavailability of Eudragit-coated PPOP compared to CA-coated ones was 106.9%, demonstrating good bioequivalence. Both of their in vitro-in vivo correlation (IVIVC) showed linear relationship, with R(2) being 0.9955 (Eudragit-coated PPOP) and 0.9987 (CA-coated PPOP), respectively. These results suggested that PPOP coated with Eudragit(®) RL 30D and RS 30D could overcome drawbacks of organic solution coating and promote the development of PPOP.

[Anti-tumor activity of folate receptor targeting docetaxel-loaded membrane-modified liposomes].

The anti-tumor activity of folate receptor targeting docetaxel-loaded membrane-modified liposomes (FA-PDCT-L) was investigated in vitro and in vivo. FA-PDCT-L was prepared by organic solvent injection method. Transmission electron microscope, dynamic light scattering and electrophoretic light scattering were employed to study the physicochemical parameters of FA-PDCT-L. The inhibitory effects of docetaxel injection (DCT-I), non-modified DCT liposomes (DCT-L) and FA-PDCT-L on the growth of MCF-7 and A-549 cells at different incubation times were detected by CCK-8 assay; and the hemolytic test was employed in vitro. Tumor mice were randomized into 4 groups: DCT-I, DCT-L, FA-PDCT-L and control group (normal saline), and given drugs at 10 mg x kg(-1) x d(-1) through tail vein. The tumor volume, mice weight, inhibition rate of tumor and life span were measured at the end of experiments. The IC50 of the FA-PDCT-L for MCF-7 and A549 cell lines were significantly lower than that of DCT-I and DCT-L, without hemolysis reaction observed. Compared with control group, the weights of tumor in DCT-I, DCT-L and FA-PDCT-L were decreased, especially for FA-PDCT-L, with inhibitory rates at 79.03 % (P < 0.05). The life span and median survival time of FA-PDCT-L treated mice were significantly higher than that of DCT-I and DCT-L. In conclusion, FA-PDCT-L shows a good anti-tumor activity, indicating that it is potential carriers for DCT in the treatment of tumor.

[Preparation of valsartan nanosuspensions and its in vitro dissolution].

To increase the dissolution rate and extent of valsartan, valsartan nanosuspensions have been prepared. Controlled precipitation assisted with sonication is utilized to prepare valsartan nanosuspensions, the concentration of the drug, stabilizer and costablizer had a great effect on the stability of the preparation according to the pre-experiment. So the method of central composite design-response surface is used to optimize the prescription based on the above three factors and the particle size as the response value. The software Origin 8.0 is used to draw the view of the three-dimensional effects and 2D contour map, to get the optimal prescription area. Valsartan nanosuspensions were prepared. The mean diameter and zeta potential are about 216.6 nm and -57.7 mV, respectively. Compared with the microsuspensions and commercial preparation, the dissolution of valsartan nanosuspensions was faster and the bioavailability can be enhanced to some extent.

[Intestinal absorption kinetics of flurbiprofen in rats].

To study the in situ intestinal absorption kinetics of flrubiprofen in rats, the absorption of flurbiprofen in small intestine (duodenum, jejunum and ileum) and colon of rats was investigated using in situ single-pass perfusion method and the drug content was measured by HPLC. The effects of drug concentration on the intestinal absorption were investigated. The K(a) and P(app) values of flurbiprofen in the small intestine and colon had no significant difference (P > 0.05). Drug concentration (4.0, 10.0 and 16.0 mg x L(-1)) had no significant influence on the K(a) values (P > 0.05). However, when concentration was 4.0 mg x L(-1) and 10.0 mg x L(-1), significant effect on the P(app) values (P < 0.05) was found, but significant effect on the P(app) values was not shown between 10.0 mg x L(-1) and 16.0 mg x L(-1) (P > 0.05). The K(a) and P(app) values of flurbiprofen on the perfusion flow rate had significant difference (P < 0.05). Flurbiprofen could be absorbed at all segments of the intestine in rats and had no special absorption window. The absorption of flurbiprofen complies with the facilitated diffusion in the general intestinal segments, and accompany with the cytopsistransport mechanism probably. The perfusion flow rate had significant effect on the K(a) and P(app).

[Formulation optimization of ginkgo flavonoids matrix tablets by orthogonal design].

Sustained-release tablet has become one of the hottest research spots in the area of sustained release preparations with its unique advantages. At present, a series of shortcomings were exited in the ordinary ginkgo preparations, which were used for the treatment of cardiovascular and cerebrovascular diseases. In order to avoid these shortcomings, ginkgo flavonoids matrix tablets were prepared in this paper. Furthermore, the amount and varieties of matrix material, adhesives and fillers were investigated. Meanwhile, the formulation was optimized by using the method of orthogonal design, and Zero-order, First-order, Higuchi, Ritger-peppas equation were used for the model fitting and mechanism discussing of drug release.

Preparation and characterization of 5-fluorouracil pH-sensitive niosome and its tumor-targeted evaluation: in vitro and in vivo.

The purpose of this study was to investigate preparation, characterization and tumor-targeted effect of pH-sensitive niosomes, composed of a nonionic surfactant mixed with cholesteryl hemisuccinate (CHEMS), a derivative of cholesterol (CHOL), as a pH-sensitive molecule. CHEMS was synthesized with CHOL and succinic acid, the structure of which was analyzed by Mass spectrometry (MS) and ¹H Nuclear magnetic resonance (¹H NMR) spectrum. Niosomes were prepared via film hydration-probe ultrasound method. Both normal niosomes and pH-sensitive niosomes showed spherical morphology under transmission electron microscope (TEM) with a average particle sizes of 172 ± 6.2 nm and 153 ± 4.7 nm, respectively. The thermotropic behavior, structure changes and interaction of 5-fluorouracil (5-Fu) with other materials were characterized by differential scanning calorimetry (DSC), and the disappearance of the melting peak of drug revealed the fact that drug was encapsulated in niosomes. Bulk-equilibrium reverse-dialysis method was chosen to investigate the behavior of drug release from normal niosomes and pH-sensitive niosomes in different pH medium, and the results showed that the noisome containing CHEMS had a pH-sensitive property. Tumor-targeted effect was proved by the fact that pH-sensitive niosomes showed a remarkable high concentration in tumor site of the mice transplanted with tumor cell.

[Preparation and in vitro properties of folate receptor targeting docetaxel-loaded amphiphilic copolymer-modified liposomes].

A novel amphiphilic copolymer, folate-poly (PEG-cyanoacrylate-co-cholesteryl cyanoacrylate) (FA-PEG-PCHL) was synthesized as liposomal modifying material with folate receptor targeting and long circulating property. FA-PEG-PCHL-modified docetaxel-loaded liposomes (FA-PDCT-L) were prepared by organic solvent injection method, and the system was optimized using central composite design-response surface methodology. The structure of the FA-PEG-PCHL copolymer was confirmed by FT-IR and 1H NMR. Ultrafiltration technique, transmission electron microscope, dynamic light scattering and electrophoretic light scattering, and fluorescence polarization method were used to study the physicochemical parameters of FA-PDCT-L. FA-PDCT-L showed spherical or ellipsoid shape. The mean particle sizes were in the range of 111.6-126.9 nm, zeta potentials were from -6.54 mV to -14.13 mV and the drug encapsulation efficiency achieved 97.8%. The observed values agreed well with model predicted values. The membrane fluidity increased with the increment of the molecular weight of PEG and the decrement of the amount of FA-PEG-PCHL. The in vitro release test showed that the drug could be sustained-released from liposomes without a burst release and with stability for 6 months. After 24 h only 31.1%, 27.2% and 19.5% of encapsulated docetaxel were released for FA-PDCT10000-L, FA-PDCT4000-L and FA-PDCT2000-L, respectively. This work is useful for further research on the application of the synthesized copolymer-modified long circulating liposomes for cancer therapy.

A novel paclitaxel microemulsion containing a reduced amount of Cremophor EL: pharmacokinetics, biodistribution, and in vivo antitumor efficacy and safety.

The purpose of this study was to prepare a novel paclitaxel (PTX) microemulsion containing a reduced amount of Cremophor EL (CrEL) which had similar pharmacokinetics and antitumor efficacy as the commercially available PTX injection, but a significantly reduced allergic effect due to the CrEL. The pharmacokinetics, biodistribution, in vivo antitumor activity and safety of PTX microemulsion was evaluated. The results of pharmacokinetic and distribution properties of PTX in the microemulsion were similar to those of the PTX injection. The antitumor efficacy of the PTX microemulsion in OVCRA-3 and A 549 tumor-bearing animals was similar to that of PTX injection. The PTX microemulsion did not cause haemolysis, erythrocyte agglutination or simulative reaction. The incidence and degree of allergic reactions exhibited by the PTX microemulsion group, with or without premedication, were significantly lower than those in the PTX injection group (P < .01). In conclusion, the PTX microemulsion had similar pharmacokinetics and anti-tumor efficacy to the PTX injection, but a significantly reduced allergic effect due to CrEL, indicating that the PTX microemulsion overcomes the disadvantages of the conventional PTX injection and is one way of avoiding the limitations of current injection product while providing suitable therapeutic efficacy.

Optimization and characterization of dry powder of fanhuncaoin for inhalation based on selection of excipients.

In this study, dry powder formulations for inhalation of fanhuncaoin, a newly discovered antiinflammatorily active compound isolated from Chinese herb, were designed to optimize the composition and further explore the relationship between the composition, the physical properties and the aerosolization performance. Dry powders were prepared by spray-drying using leucine, chitosan, chitosan oligosaccharide and dipalmitoyl phosphatidylcholine (DPPC) as excipients. Following spray-drying, resultant powders were characterized using scanning electron microscopy, tapped density analysis, laser diffractometry, thermogravimetric analysis and differential scanning calorimetry. The aerosol behaviour of the powders was studied in a Twin Stage Impinger at an airflow rate of 60 l/min using a HandiHaler® inhaler device. Results revealed that the nature and the relative proportion of the excipients greatly influenced the physical characteristics of the powders and their aerodynamic behavior. Among the combinations tested, the composition ratio of fanhuncaoin/leucine/chitosan/chitosan oligosaccharide/DPPC of 10/45/33.75/11.25/0.4 (w/w/w/w/w) prepared in a total solid mass of 1% (w/v) formulation was found to be particularly optimal and exhibited a tapped density of 0.44 g/cm³, an aerodynamic diameter of 2.24 µm and an respirable fraction of 51.29%. In conclusion, optimization of the aerosolization properties of inhalation dry powders could be achieved by appropriately selecting the composition of the particles.

Preparation and in vitro release of dual-drug resinate complexes containing codeine and chlorpheniramine.

OBJECTIVE: To develop the dual-drug resinate complexes containing codeine and chlorpheniramine with a novel batch processing, characterize the dual-drug resinate complexes, and study its drug release behavior in vitro. METHODS: A procedure of simultaneous dual-drug loading using combination solutions composed of different proportions of codeine phosphate and chlorpheniramine maleate was performed to achieve the specific resinate, and the dual-drug loading content was determined by high-performance liquid chromatography method. The dual-drug resinate complexes were characterized by a scanning electron microscope, and the formation mechanisms were confirmed with X-ray diffraction analyses and differential scanning calorimetric analyses. The release behavior of the two drugs from the dual-drug resinate complexes in vitro was studied in the media simulating in vivo environments (simulated gastric fluid: pH = 1.2 HCl, simulated in vivo ionic strength: 0.15 M NaCl, and simulated intestinal fluid: pH = 6.8 buffer solution containing KH2PO4-NaOH). RESULTS: Scanning electron microscopic analyses proved that the dual-drug resinate complexes had the same appearance and characters as the initiative ion exchange resins (IERs). Via X-ray diffraction and differential scanning calorimetric analyses, it is found that the two drugs in dual-drug resinate complexes were combined with IERs by chemical bond. The drug-resinate complex, like IER, was in amorphous state. More than 90% of codeine phosphate was released in 15 minutes in three different media, whereas little amount of chlorpheniramine maleate was released in all the release time in the medium pH = 1.2 HCl, and the release equilibrium time was about 5 minutes, only 40% was released in the medium 0.15 M NaCl, and the equilibrium time was 40 minutes, and about 90% was released in the medium pH = 6.8 KH2PO4-NaOH. The increased ionic strength generally accelerated the release of the two drugs from the dual-drug resinate complexes. CONCLUSION: The dual-drug resinate complexes were formed through the reaction between the drugs and the IERs by chemical bond. The release behavior of the drug from the dual-drug resinate complexes in vitro was mainly correlated with the drug molecular structure, the eluting ionic strength, composition, and ionic strength of the release media. The novel dual-drug resinate complexes could be used to deliver two drugs in one therapeutic dose.

[Comparison of the characteristics of several polymer materials used in hydrophilic matrix tablets].

Pure and drug hydrophilic matrix tablets were prepared by direct compression method with theophylline as a model drug. The characteristics of four hydrophilic matrix polymers, hydroxypropylmethylcellulose (HPMC), polyethylene oxide (PEO), sodium alginate (NaAlg) and xanthan gum (XG), were compared by investigating the water absorption, swelling, erosion and gel layer strength. The sequence of water absorption rate was XG >> NaAlg (H) > PEO > NaAlg (L) >> HPMC; The sequence of swelling index was XG >> PEO >> HPMC >> NaAlg; The sequence of erosion rate was NaAlg (L) > NaAlg (H) >> PEO80 > PEO200 > PEO300 > XG approximately PEO400 approximately K4M > K15M > PEO600 approximately K100M; The sequence of the gel layer strength was PEO > HPMC > XG >> NaAlg. For the PEO and HPMC matrix tablets, with the polymer molecular weight increased, the drug release mechanism was gradually transferred from mainly depending on the erosion to the diffusion; for SAL matrix tablets, the drug release mainly depends on erosion mechanism; and for XG matrix tablets, the drug release mainly depends on non-Fick diffusion mechanism. Comparison of the performance difference between the polymer materials will contribute to rational design and prediction of drug release behaviors from matrix tables and ultimately to achieve clinical needs.

[Design push-pull osmotic pump tablets of famotidine based on an expert system for the formulation design of osmotic pump of poor water-soluble drug].

The purpose of this study is to design push-pull osmotic pump (PPOP) tablets of famotidine using the expert system for the formulation design of osmotic pump of poor water-soluble drug which had been established by the authors. Firstly, the parameters which were requisite of the system input were obtained from literatures and experimental tests. Then the parameters were input into the system, and the program was run. The system displayed the designed formulations sequential. Finally, famotidine PPOP was prepared according to the designed formulations and the in vitro dissolution was carried out. It was found out that the target formulation of famotidine PPOP which could release for 24 hours was obtained in a very short period. Meanwhile, the practicability of the established expert system was proved.

Preparation and evaluation of self-microemulsifying drug delivery system containing vinpocetine.

The main purpose of current investigation is to prepare a self-microemulsifying drug delivery system (SMEDDS) to enhance the oral bioavailability of vinpocetine, a poorly water-soluble drug. Suitable vehicles were screened by determining the solubility of vinpocetine in them. Certain surfactants were selected according to their emulsifying ability with different oils. Ternary phase diagrams were used to identify the efficient self-microemulsifying region and to screen the effect of surfactant/cosurfactant ratio (K(m)). The optimized formulation for in vitro dissolution and bioavailability assessment was oil (ethyl oleate, 15%), surfactant (Solutol HS 15, 50%), and cosurfactant (Transcutol P, 35%). The release rate of vinpocetine from SMEDDS was significantly higher than that of the commercial tablet. Pharmacokinetics and bioavailability of SMEDDS were evaluated. It was found that the oral bioavailability of vinpocetine of SMEDDS was 1.72-fold higher as compared with that of the commercial tablet. These results obtained demonstrated that vinpocetine absorption was enhanced significantly by employing SMEDDS. Therefore, SMEDDS might provide an efficient way of improving oral bioavailability of poorly water-soluble drugs.

[Optimization of a floating osmotic pump system of dipyridamole using central composite design-response surface methodology].

A new type of floating osmotic pump of dipyridamole was designed in this paper. Apparatus three (Chinese Pharmacopeia 2005, appendix XD) was employed for in vitro dissolution test in order to evaluate the release and floating behavior in a same experiment. The system was optimized using central composite design-response surface methodology; where similarity factor (f2) between the dissolution profile of prepared formulation and the target dissolution profile was taken as dependent factor, usage amount of polyoxyethylene (X1, mg), NaCl (X2, mg) and pore former (PEG4000, X3, %) were taken as independent factors. The optimization model was f2 = -29.3 + 2.35X3 - 0.123X1(2) - 0.046X2(2) + 0.145X1X2 (R = 0.996). It was found that the dissolution profile could match the target dissolution profile under the condition of weight gain 8%-9%, X1 (20-34), X2 (30-57), X3 = 50. It is also found that the minimum usage percentage of pore former is 35.1%. The prediction results of the optimization model were good in the experiments.

Effects of breast cancer resistance protein inhibitors and pharmaceutical excipients on decreasing gastrointestinal toxicity of camptothecin analogs.

AIM: To investigate the effect of breast cancer resistance protein (BCRP) inhibitors and pharmaceutical excipients on reducing the biliary excretion of camptothecins (CPT), ameliorating delayed-type diarrhea and intestinal mucosa damage induced by CPT. METHODS: The cumulative biliary excretion of irinotecan (CPT-11) and hydroxycamptothecin (HCPT) with or without BCRP inhibitors and excipients was investigated in rats. The gastrointestinal toxicity, assessed as the diarrheal score, body weight change and microscopic pathological damage was also determined in rats. RESULTS: Breast cancer resistance protein (BCRP) exhibited important effects on the biliary excretion of CPT. Coadministration of BCRP inhibitors such as GF120918 and cyclosporin A reduced the biliary excretion of CPT-11 and HCPT. Pharmaceutical excipients such as Pluronic F68 and PEG 2000 stearate also showed inhibitory effects on BCRP and similarly reduced CPT biliary excretion. The observed gastrointestinal toxicity was ameliorated by coadministration of BCRP inhibitors and excipients compared with injection of CPT-11 and HCPT alone. CONCLUSION: The use of excipients as inhibitors of BCRP is safe and relatively non-toxic, and may lead to important pharmacotherapeutic benefits by decreasing the gastrointestinal toxicity of CPT.

Pluronic F127-g-poly(acrylic acid) copolymers as in situ gelling vehicle for ophthalmic drug delivery system.

To prolong the precorneal resident time and improve ocular bioavailability of the drug, Pluronic F127-g-poly(acrylic acid) copolymers were studied as in situ gelling vehicle for ophthalmic drug delivery system. The rheological properties and in vitro drug release of Pluronic-g-PAA copolymer gels were investigated. The rheogram and in vitro drug release studies indicated that the drug release rates decreased as acrylic acid/Pluronic molar ratio and copolymer solution concentration increased. But the drug concentration had no obvious effect on drug release. The release rates of the drug from such copolymer gels were mainly dependent on the gel dissolution. In vivo resident experiments showed the drug resident time and the total resident amount in rabbit's conjunctiveal sac increased by 5.0 and 2.6 folds for in situ gel, compared with eye drops. The decreased loss angle at body temperature and prolonged precorneal resident time also indicated that the copolymer gels had bioadhesive properties. These in vivo experimental results, along with the rheological properties and in vitro drug release studies, demonstrated that in situ gels containing Pluronic-g-PAA copolymer may significantly prolong the drug resident time and thus improve bioavailability. Pluronic-g-PAA copolymer can be a promising in situ gelling vehicle for ophthalmic drug delivery system.

A controlled-release ocular delivery system for ibuprofen based on nanostructured lipid carriers.

The objective of this study was to develop an ocular drug delivery system based on nanostructured lipid carrier and investigate its in vitro and in vivo characteristics. Ibuprofen was chosen as the model drug. Four different formulations of ibuprofen nanostructured lipid carriers were prepared by melted-ultrasonic methods; gelucire 44/14 was screened as one of the solid lipid matrix materials due to the good particle size dispersion and excellent contribution to the corneal permeability of the model drug. The modified Franz-type diffusion cells and isolated corneas were used in the test of drug corneal permeability and the in vivo releasing tests were carried out using microdialysis method. gelucire 44/14 and transcutol P could enhance the corneal permeability by different mechanisms. The corresponding apparent permeability coefficients (P(app)) were 1.28 and 1.36 times more than that of the control preparation. Stearylamine could prolong the pre-cornea retention time of the model drug to some extent. Ibuprofen nanostructured lipid carriers displayed controlled-release property. The AUC of the optimized formulation of ibuprofen nanostuctured lipid carriers was 3.99 times more than that of ibuprofen eye drops).

[Effects of in vitro conditions on release behavior of different types of sustained and controlled release formulations of breviscapin].

Insoluble breviscapin was chosen as the model drug. Bi-layer osmotic pump technology and gel matrix technology were used to prepare the breviscapin sustained and controlled release preparations. Dissimilarity factors (f1) and similarity factors (f2) were applied as similar judgment index to compare the effects of in vitro conditions on the release behavior of different types of breviscapin sustained and controlled release preparations. The tolerance of in vitro release conditions of bi-layer osmotic pump technology and gel matrix technology were studied. The results showed that in vitro release conditions have a greater impact on the gel matrix sustained release formulations, while have almost no effects on the osmotic pump controlled release formulations. Therefore, osmotic pump controlled release technology is less affected by the drug release environment. And it has a very good application prospect.