共查询到12条相似文献,搜索用时 15 毫秒
1.
Sun M Sun J He S Wang Y Sun Y Liu X He Z 《Drug development and industrial pharmacy》2012,38(9):1099-1106
In this study, a new discriminative dissolution condition for lacidipine tablets was developed by the established in vitro-in vivo relationship. Series of dissolution media of phosphate buffer solution (PBS) covering the pH range of 1-7.2 and pH 6.8 PBS containing different concentrations of sodium dodecyl sulfate (SDS), were prepared and used to investigate the dissolution behavior of lacidipine tablets. There was an obvious difference in the dissolution profiles of the both brands in pH 6.8 PBS medium containing 0.1% SDS. The pharmacokinetic study of the two lacidipine tablets was carried out in the healthy beagle dogs at a single dose of 4 mg. Statistical comparison of the AUC(0-24), C(max), and T(max) showed a significant difference in the two brand tablets, coinciding with the dissolution performance with pH 6.8 PBS containing 0.1% SDS. The superiority of the proposed system, pH 6.8 PBS containing 0.1% SDS, could serve as a dissolution medium for lacidipine tablets, and more important it could discriminate the in vivo pharmacokinetic behavior for different brands of products. In summary, in vivo pharmacokinetic evaluation is essential to develop an appropriate in vitro dissolution condition for oral solid dosage forms of poorly soluble drugs. 相似文献
2.
《Drug development and industrial pharmacy》2013,39(6):889-900
Objective: The suitability of the rabbit as an animal model for the primary screening and selection of the pilot scale batches during the early stages of the formulation development was studied.Materials and methods: Three modified-release formulations of aminophylline consisted of Carbopol® 971P/HPMC K4M (F-I), and HPMC K100M (F-II) or HPMC K4M (F-III) were used. Commercial products were Aminofilin retard 350?mg tablets, Srbolek, Serbia (R-I) and Phyllocontin® 350, tablets Purdue Frederic, Canada (R-II).Results: Calculated release rate constants and the ?2 values between R-I/F-I (84.1) and R-II/F-III (83.4) indicated similar in vitro release while the coefficient n showed presence of different mechanisms of release from Anomalous transport, Fickian diffusion to Case-II transport. Higher Tmax, was found in the rabbits, dosed with F-II (12.00?h), F-III (10.50?h), and R-II (15.00?h) formulation. The highest Cmax (9.22?mg/L) was obtained with F-II, similar lower values was seen for F-I and F-III, while commercial products showed the lowest values R-I (5.58?mg/L) and R-II (4.18?mg/L). Higher AUC values were detected for all three formulations (from 115.90 to 204.06 mgh/L) in relation to commercial products (105.33 and 113.25 mgh/L).Discussion and conclusion: The results demonstrated a good correlation of Level A (r2 = 0.97) for the two formulations (F-I, F-III) and commercial product (R-I) indicates that there is a reasonable assumption that the rabbit might be use as a model for the preliminary comparison of scale up formulations in the early stages of the product development. 相似文献
3.
Fujisaki Y Tsukune T Funyû M Okumura M Ukigaya T Sugibayashi K 《Drug development and industrial pharmacy》2006,32(2):207-217
We have developed a 200 mg and 400 mg sustained-release sodium valproate tablet that allows effective blood concentration of the active drug with once-a-day dosing. The controlled dissolution or sustained release of the drug was attained by a membrane-controlled system. A single-coating system did not adequately control the dissolution rate, and therefore double-coated tablets were prepared and a human pharmacokinetic study was conducted. With the 200 mg VPA-Na tablets, the nonfasting Cmax was only 20% higher than the fasting Cmax. An in vitro dissolution test was conducted to predict the effects of food on drug dissolution after administration of this tablet. A relatively good correlation was observed between the absorption profiles and the dissolution profiles of the drug. 相似文献
4.
Nini Li Ling Fan Biao Wu Genlai Dai Chengjun Jiang Yan Guo 《Drug development and industrial pharmacy》2013,39(7):1079-1088
The objective of this study was to design and evaluate azilsartan osmotic pump tablets. Preformulation properties of azilsartan were investigated for formulation design. Azilsartan osmotic pump tablets were prepared by incorporation of drug in the core and subsequent coating with cellulose acetate and polyethylene glycol 4000 as semi-permeable membrane, then drilled an orifice at the center of one side. The influence of different cores, compositions of semipermeable membrane and orifice diameter on azilsartan release were evaluated. The formulation of core tablet was optimized by orthogonal design and the release profiles of various formulations were evaluated by similarity factor (f2). The optimal formulation achieved to deliver azilsartan at an approximate zero-order up to 14?h. The pharmacokinetic study was performed in beagle dogs. The azilsartan osmotic pump tablets exhibited less fluctuation in blood concentration and higher bioavailability compared to immediate-release tablets. Moreover, there was a good correlation between the in vitro dissolution and in vivo absorption of the tablets. In summary, azilsartan osmotic pump tablets presented controlled release in vitro, high bioavailability in vivo and a good in vitro-in vivo correlation. 相似文献
5.
Yali Liu Peng Li Rong Qian Tianyu Sun Fangzhi Fang Zonghua Wang 《Drug development and industrial pharmacy》2018,44(8):1317-1327
6.
Controlled release bi-layer osmotic pump tablets (BOPT) of water—insoluble allopurinol with large dose (150 mg/BOPT) were successfully prepared merely with sodium chloride as osmotic promoting agent and polyethylene oxide (PEO) as suspending agent. Formulations of the two kinds of agents were investigated in order to discuss their effects on the release behavior of BOPT, and then the optimal formulation was evaluated. The pharmacokinetics studies of allopurinol and its active metabolite oxypurinol in two-preparation and two-period crossover design relative to the equivalent dose of commercially common allopurinol tablets were evaluated in six Beagle dogs. And the pharmacokinetics results showed that allopurinol BOPT were able to provide a slow release of allopurinol, and oxypurinol were bioequivalent between allopurinol BOPT and common allopurinol tablets. A good in vitro-in vivo correlation of allopurinol was also proved. In conclusion, water-insoluble drugs with large dose can be designed to BOPT for efficacy and safety use. 相似文献
7.
Solid dispersions of Celecoxib were prepared with hydroxypropyl β cyclodextrin by various methods such as physical mixture, cogrinding, kneading, and coevaporation. The dispersions were characterized by differential scanning calorimetry (DSC), X-ray diffraction patterns, infrared spectroscopy, and nuclear magnetic resonance studies. The DSC thermograms of the dispersions indicated potential of heat-induced interaction between Celecoxib and cyclodextrin that could influence in vitro drug dissolution. The dispersions exhibited faster rates of dissolution compared to that of Celecoxib. The kneaded dispersion with the fastest in vitro dissolution rate when compressed into tablets showed a better release profile compared to the tablets of pure Celecoxib. In vivo studies revealed that the kneaded dispersion provided for quicker response and was more effective in inhibiting rat paw edema as compared to Celecoxib alone, thus confirming the advantage of improved pharmacological activity of Celecoxib when administered as a solid dispersion with cyclodextrin. 相似文献
8.
《Drug development and industrial pharmacy》2013,39(3):447-456
Objective: The aim of this study was to develop chronotherapeutic drug delivery system of indomethacin using polyethylene oxide (PEO) with a predetermined lag time of 6 h by compression coating technique.Materials and methods: Solid dispersions (SD) of indomethacin were prepared using novel carrier sucrose fatty acid ester (SFE 1815) to increase the in vitro dissolution. The optimized SD was formulated as immediate release core tablet which were further coated with PEO (WSR Coagulant or WSR N12 K) using compression coating technique. Compression coated tablets formulated with PEO WSR Coagulant in 1:1.7 ratio of core tablet weight and coating polymer was considered as optimized formulation, which was further characterized by differential scanning calorimetry, X-ray diffractometry, Fourier transformed infrared spectroscopy, and scanning electron microscopy.Results: The results indicated that there was no chemical incompatibility and slight change in surface properties. Cmax, area under the curve (AUC0-t), and Tmax following oral ingestion of commercial capsule (Indocap) and optimized formulation (CT 4) were found to be 1973.18 ± 36.89 ng/mL, 11090.09 ± 131.21 ng/mL/h, 0.99 ± 0.02 h and 2115.46 ±6 2.61, 10413.14 ± 299.66 ng/mL/h, 7.00±0.02 h, respectively.Conclusion: Unaltered AUC0-t and Cmax, but delayed Tmax indicated clear lag time before immediate release of drug which is suitable for treating rheumatoid arthritis following circadian rhythm. 相似文献
9.
Huang YT Tsai TR Cheng CJ Cham TM Lai TF Chuo WH 《Drug development and industrial pharmacy》2007,33(11):1183-1191
Pyridostigmine bromide (PB), a highly hygroscopic drug was selected as the model drug. A sustained-release (SR) tablet prepared by direct compression of wet-extruded and spheronized core pellets with HPMC excipients and exhibited a zero-order sustained release (SR) profile. The 23 full factorial design was utilized to search an optimal SR tablet formulation. This optimal formulation was followed zero-order mechanism and had specific release rate at different time intervals (released % of 1, 6, and 12 hr were 15.84, 58.56, and 93.10%). The results of moisture absorption by Karl Fischer meter showed the optimum SR tablet could improve the hygroscopic defect of the pure drug (PB). In the in vivo study, the results of the bioavailability data showed the Tmax was prolonged (from 0.65 ± 0.082 hr to 4.83 ± 1.60 hr) and AUC0-t (from 734.88 ± 230.68 ng/ml.hr to 1153.34 ± 488.08 ng/ml.hr) and was increased respectively for optimum PB-SR tablets when compared with commercial immediate release (IR) tablets. Furthermore, the percentages of in vitro dissolution and in vivo absorption in the rabbits have good correlation. We believe that PB-SR tablets designed in our study would improve defects of PB, decrease the frequency of administration and enhance the retention period of drug efficacy in vivo for personnel exposed to contamination situations in war or terrorist attacks in the future. 相似文献
10.
《Drug development and industrial pharmacy》2013,39(9):1134-1141
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. 相似文献
11.
AbstractDevelopment of extended release oral formulations of dexketoprofen trometamol (DT), a rapidly eliminated drug with high solubility, poses a great challenge especially when a portion of the dose is to be absorbed from the colon. In this study, site-specific release-retardant mini-matrix tablets (SSRRMTs) were developed and functionally coated with pH-responsive materials to achieve a site-specific delivery of DT at the duodenojejunal (DSRRMT) and ileocecal (ISRRMT) regions. Stomach-specific coated mini-tablets (SSCMTs) were manufactured for immediate release of about 16% of the daily dose of DT in the stomach. The SSCMT, DSRRMT, and ISRRMT were combined into a solid dosage form (C-SSRRMT tablets or capsules) to achieve the required linear release profile for once daily administration of DT. The SSRRMT and C-SSRRMT formulations were evaluated for the physical properties, in vitro-disintegration and in vitro dissolution and proved to be consistent with the pharmacopeial specifications. The in vitro release profiles of both C-SSRRMT tablets and capsules showed a constant release rate of about 6?mg/h and were similar to that of the theoretical target linear release profile. The pharmacokinetic study using human volunteers showed the bioequivalence of a single oral dose of C-SSRRMT capsules compared to three-successive oral doses of the immediate release market tablets with less ups and downs in the drug levels. The C-SSRRMT capsules formulation, may therefore, constitute an advance in the extended oral delivery of DT without the lack of efficacy and the adverse events frequently encountered in multiple daily dosing of the immediate release tablets. 相似文献
12.
Yuli Wang Jiahui Yang Yong Qian Meiyan Yang Yan Qiu 《Drug development and industrial pharmacy》2015,41(7):1120-1129
The objective of this study was to develop a novel ethylcellulose (EC)-coated pellet with partial active dose as a pore former for the controlled release of water-soluble metoprolol succinate (MS) without an initial lag phase (slow/non-drug release phase). MS-layered cores with a high drug-loading efficiency (97%, w/w), a smooth surface, and an acceptable level of resistance to abrasion were first obtained by spraying a concentrated drug solution (60% w/w at 70?°C) on non-pareils in the absence of other binders. The presence of the drug in an EC coating solution significantly improved the coating process by reducing pellet stickiness. Central composite design and response surface methodology was employed to optimize and explore the effect of pore former MS level (X1) and EC coating level (X2) on the drug release. The pore former level had a positive effect on the MS release and the coating level had a negative effect. The level of X1 and X2 of the optimization were 17% and 23%, respectively, and the cumulative percent of MS released within 1?h was up to 9.2%. Accordingly, the initial lag phase associated with in vitro drug release from EC-coated pellets was absent when MS drug was used as a pore former, which was further confirmed by in vivo drug release in beagle dogs. Thus, a novel approach for the controlled release of MS from coated pellets without lag phase has been successfully developed, which is valuable for the advancement of sustained-release pellets. 相似文献