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1.
The potential of hydrophilic aerogel formulations and liquisolid systems to improve the release of poorly soluble drugs was investigated using griseofulvin as model drug. The in vitro release rates of this drug formulated as directly compressed tablets containing crystalline griseofulvin were compared to aerogel tablets with the drug adsorbed onto hydrophilic silica aerogel and to liquisolid compacts containing the drug dissolved or suspended in PEG 300. Furthermore, the commonly used carrier and coating materials in liquisolid systems Avicel® and Aerosil® were replaced by Neusilin®, an amorphous magnesium aluminometasilicate with an extremely high specific surface area of 339 m2/g to improve the liquisolid approach.Both the liquisolid compacts containing the drug dissolved in PEG 300 and the aerogel tablets showed a considerably faster drug release than the directly compressed tablets. With liquisolid compacts containing the drug suspended in PEG 300, the release rate increased with rising fraction of dissolved drug in the liquid portion. It could be shown that Neusilin® with its sevenfold higher liquid adsorption capacity than the commonly used Avicel® and Aerosil® allows the production of liquisolid formulations with lower tablet weights.  相似文献   

2.
Liquisolid systems were originally designed to enhance dissolution of hydrophobic drugs. Recently, the same technique was explored to control drug release via hydrophobic carriers. This work aimed to study the effects of different liquid vehicles on release characteristics of griseofulvin as a model hydrophobic drug. Fast dissolution tablets were prepared using three different non-ionic surfactants namely Cremophor(?)EL, Synperonic(?)PE/L61 and Capryol? 90, on the contrary Kollicoat(?)SR 30D was used for production of grieseofulvin sustained release formulations. Avicel(?) PH102 and Cab-O-Sil(?) M5 were used as carrier and coat materials, respectively. The effect of formulation parameters, such as drug concentration and carrier to coat ratio, on enhancing drug dissolution was explored. Drug concentrations of 20% and 40% (w/w), and R-values (carrier to coat ratio) of 10 and 20 were used. The mathematical model was utilized to formulate liquisolid powder systems. All fast release liquisolid formulations showed higher percentage drug dissolution efficiency (%DE) than conventional directly compacted tablets. Cremophor(?)EL showed the best dissolution enhancement with %DE of about 90%, compared to only 23% for conventional tablets; DSC data suggested loss of griseofulvin crystallinity and thermal behavior. Kollicoat(?) SR 30D retarded the drug release even in the presence of hydrophilic carrier; DSC data suggested that only small fraction of the drug was present in the molecular state within the system. The used liquisolid vehicles showed promise to enhance and to control (depend on the choice of the liquid vehicle) the release of griseofulvin from liquisolid compacts.  相似文献   

3.
A liquisolid system has the ability to improve the dissolution properties of poorly water soluble drugs. Liquisolid compacts are flowing and compactable powdered forms of liquid medications. The aim of this study was to enhance the in vitro dissolution properties of the practically water insoluble loop diuretic furosemide, by utilising liquisolid technique. Several liquisolid tablets were prepared using microcrystalline cellulose (Avicel® pH-101) and fumed silica (Cab-O-Sil® M-5) as the carrier and coating materials, respectively. Polyoxy-ethylene-polyoxypropylene-polyoxyethylene block copolymer (Synperonic® PE/L 81); 1,2,3-propanetriol, homopolymer, (9Z)-9-octadecenoate (Caprol® PGE-860) and polyethylene glycol 400 (PEG 400) were used as non- volatile water-miscible liquid vehicles. The liquid loading factors for such liquid vehicles were calculated to obtain the optimum amounts of carrier and coating materials necessary to produce acceptable flowing and compactible powder admixtures viable to produce compacts. The ratio of carrier to coating material was kept constant in all formulations at 20 to 1. The formulated liquisolid tablets were evaluated for post compaction parameters such as weight variation, hardness, drug content uniformity, percentage friability and disintegration time. The in-vitro release characteristics of the drug from tablets formulated by direct compression (as reference) and liquisolid technique, were studied in two different dissolution media. Differential scanning calorimetry (DSC) and Fourier-Transform infrared spectroscopy (FT-IR) were performed. The results showed that all formulations exhibited higher percentage of drug dissolved in water (pH 6.4–6.6) compared to that at acidic medium (pH 1.2). Liquisolid compacts containing Synperonic® PE/L 81 demonstrated higher release rate at the different pH values. Formulations with PEG 400 displayed lower drug release rate, compared to conventional and liquisolid tablets. DSC and FT-IR indicated a possible interaction between furosemide and tablet excipients that could explain the dissolution results. Caprol® PGE-860, as a liquid vehicle, failed to produce furosemide liquisolid compacts.  相似文献   

4.
Ahmed Khames 《Drug delivery》2017,24(1):328-338
BCS class II drugs usually suffer inadequate bioavailability as dissolution step is the absorption rate limiting step. In this work, the effect of solubility increase at the main absorption site for these drugs was investigated using risperidone as a drug model. Liquisolid technique was applied to prepare risperidone per-oral tablets of high dissolution rate at intestinal pH (6.8) using versatile nonionic surfactants of high solubilizing ability [Transcutol HP, Labrasol and Labrasol/Labrafil (1:1) mixture] as liquid vehicles at different drug concentrations (10–30%) and fixed (R). The prepared liquisolid tablets were fully evaluated and the dissolution rate at pH 6.8 was investigated. The formulae that showed significantly different release rate were selected and subjected to mathematical modeling using DE25, MDT and similarity factor (f2). Depending on mathematical modeling results, formula of higher dissolution rate was subjected to solid state characterization using differential scanning calorimetric (DSC), infrared spectroscopy (IR) and X-ray diffraction (XRD). Finally, the drug bioavailability was studied in comparison to conventional tablets in rabbits. Results showed that liquisolid tablet prepared using Labrasol/Labrafil (1:1) mixture as liquid vehicle containing 10% risperidone is a compatible formula with law drug crystallinity and higher dissolution rate (100% in 25?min). The drug bioavailability was significantly increased in comparison to the conventional tablets (1441.711?μg h/mL and 137.518?μg/mL in comparison to 321.011?μg h/mL and 38.673?μg/mL for AUC and Cpmax, respectively). This led to the conclusion that liquisolid technique was efficiently improved drug solubility and solubility increase of BCS class II drugs at their main absorption site significantly increases their bioavailability.  相似文献   

5.
Context: Liquisolid technique is one of the methods used to improve the dissolution rate of the poorly water soluble drugs utilizing non volatile liquids.Objectives: Enhancement of the release of ezetimibe from different liquisolid formulations.Materials and Methods: Four liquid vehicles were used to prepare the liquid medications with different drug concentrations. The interaction between the drug and the excipients in liquisolid powders were characterized by DSC, X-ray, FTIR and SEM. Furthermore, the powder characteristics were evaluated by Carr’s Index and powder wetting time determinations, respectively. All prepared formulations were compressed at different pressures to end with the same constant porosity and the tablets were evaluated by different tests and compared with conventional formula. Results and Discussion: No interaction had been detected in all liquisolid formulations as shown in the results of XRD, FTIR, DSC and SEM. In addition to that, all liquisolid compacts had expressed faster dissolution profiles compared with that of conventional formula. Conclusion: The dissolution rate was affected by the drug concentration, solubility of the drug in the liquid vehicle and type of carrier. In addition, the presence of the liquid vehicle has been found to affect the mechanical properties of the liquisolid formulations.  相似文献   

6.
The impact of hydrogel polymers and dissolution media on tablet gel strength, Γ, of controlled release (CR) hydrogel tablets was investigated. CR tablets containing either hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), or carbomer were formulated with theophylline and Fast Flo® lactose, to produce tablets with a polymer content of 8, 15, and 30% w/w. Γ was measured using a previously reported method. The drug dissolution profiles were similar, irrespective of polymer type or dissolution media (DI water, 0.1 N HCl, and pH 6.8 phosphate buffer), at the same % w/w level of polymer. Γ, however, showed large and significant differences (p≤0.05) between tablets containing different polymers and between different dissolution media. Γ values were HPMC K100MP > HPC HXF > carbomer 971P (same % w/w) with absolute Γ values at 30% w/w in DI water of 6600, 4600, and 1600 ergs/cm3, respectively. Γ for HPMC based tablets was independent of changes in dissolution media, while the Γ values for HPC tablets were 18% lower in acid and buffer than in DI water. Of the polymers tested, carbomer based tablets had the lowest Γ values in all dissolution media and an unexpected 58% lower Γ in buffer compared with DI water or acid. Γ provides a quantitative measure of the effect of formulation and dissolution parameter changes on tablet gel layer strength, under in vitro stress conditions that may parallel in vivo tablet performance, but which cannot be deduced from a comparison of dissolution profiles or polymer viscosity.  相似文献   

7.
Purpose

To develop tablet formulations by adsorbing liquid self-emulsifying drug delivery systems (SEDDS) onto Neusilin®US2, a porous silicate.

Methods

Nine SEDDS were prepared by combining a medium chain monoglyceride, Capmul MCM EP, a medium chain triglyceride, Captex 355 EP/NF, or their mixtures with a surfactant Cremophor EL, and a model drug, probucol, was then dissolved. The solutions were directly adsorbed onto Neusilin®US2 at 1:1 w/w ratio. Content uniformity, bulk and tap density, compressibility index, Hausner ratio and angle of repose of the powders formed were determined. The powders were then compressed into tablets. The dispersion of SEDDS from tablets was studied in 250 mL of 0.01NHCl (USP dissolution apparatus; 50 RPM; 37°C) and compared with that of liquid SEDDS.

Results

After adsorption of liquid SEDDS onto Neusilin®US2, all powders demonstrated acceptable flow properties and content uniformity for development into tablet. Tablets with good tensile strength (>1 MPa) at the compression pressure of 45 to 135 MPa were obtained. Complete drug release from tablets was observed if the SEDDS did not form gels in contact with water; the gel formation clogged pores of the silicate and trapped the liquid inside pores.

Conclusion

Liquid SEDDS were successfully developed into tablets by adsorbing them onto Neusilin®US2. Complete drug release from tablets could be obtained.

  相似文献   

8.
目的:探讨液固压缩技术对α-细辛脑溶出的影响。方法:采用液固压缩技术制备α-细辛脑液固压缩片(液体赋形剂为吐温80或聚乙二醇400,载体材料为PH-101微晶纤维素,涂层材料为微粉硅胶200),与市售细辛脑片在片剂质量和溶出度方面进行比较。结果:α-细辛脑液固压缩片中α-细辛脑在短时间内迅速溶出,5 min时达到80%以上,是市售细辛脑片溶出度的3倍,且崩解时限均<100 s。结论:液固压缩技术对难溶性药物α-细辛脑的溶出有一定帮助。  相似文献   

9.
This investigation was aimed to improve the dissolution rate of the poorly soluble drug lovastatin, by formulating it as a liquisolid compact. Different liquisolid compacts were prepared using mathematical formulae to calculate the required quantities of powder and liquid ingredients to produce acceptably flowable and compressible admixture. Avicel PH 200, Cab-O-Sil, sodium starch glycolate and PEG 400 were employed as carrier, coating material, disintegrant and non-volatile liquid vehicle, respectively. The various drug to liquid and carrier to coating ratio were used to prepare liquisolid compacts. The formulated liquisolid tablets were evaluated for weight variation, hardness, drug content, friability and disintegration time. The in vitro release characteristics of the drug from tablets formulated by direct compression and liquisolid technique were compared in two different dissolution media. The tableting properties of the liquisolid compacts were within the acceptable limits and drug release rates were distinctly higher as compared to directly compressed tablets. The FTIR spectra showed no interaction between drug-excipient and disappearance of the characteristic absorption band of lovastatin in liquisolid formulations could be attributed to the formation of hydrogen bonding between the drug and liquid vehicle, which resulted in dissolution enhancement. Thus, the liquisolid technique was found to be a promising approach for improving the dissolution of a poorly soluble drug like lovastatin.  相似文献   

10.
The potential of liquisolid systems to improve the dissolution properties of a water-insoluble agent (piroxicam) was investigated. In this study, physicochemical properties of piroxicam liquisolid tablets, effect of aging, and type of the carrier were also investigated. To this end, several liquisolid tablets formulations containing various ratios of drug: solvent and different carriers were prepared. X-ray crystallography, differential scanning calorimetry (DSC), and contact angle measurement were used for evaluation of physicochemical properties of piroxicam. Liquisolid compacts exhibited significantly higher drug dissolution rates, in different dissolution media, than compacts prepared by the direct compression technique. The results showed that enhanced dissolution rate of piroxicam liquisolid tablets was due to an increase in wetting properties and surface area of drug available for dissolution. To investigate the effect of aging on the hardness and dissolution rate of liquisolid compacts, the formulations were stored at 25 degrees C/75% relative humidity for 9 months. The results showed that aging had no significant effect on hardness or dissolution profile of liquisolid tablets. It was shown that Avicel had more liquid retention potential than other carriers, but there were no significant differences in the dissolution profiles between formulations. The results of DSC and X-ray crystallography did not show any changes in crystallinity of the drug and interaction between piroxicam and exipients (Avicel and silica) during the process.  相似文献   

11.
Efavirenz displays low and variable bioavailability because of its poor aqueous solubility and high log P-value. The present investigation was aimed to improve the dissolution profile of efavirenz by using a simple, scalable and cost-effective technique of liquisolid compact. The drug was dissolved in Trancutol-HP for preparing the liquid medicament which was subsequently mixed with carrier and coating material to make free-flowing and compressible powder. 32 full factorial design was used to optimize the formulation in which the Neusilin US2/Corn starch ratios and carrier/coating material ratio were selected as independent variables. The results of in-vitro dissolution test proved that liquisolid compacts have significantly higher dissolution rate than tablets containing pure drug. Results of DSC and XRD studies suggested that the high dissolution of the drug from the liquisolid compacts was possibly because of the drug either being in an amorphous state or being molecularly dispersed within the internal matrix of compacts.  相似文献   

12.
Although famotidine was reported to be 7.5 and 20 times more potent than ranitidine and cimetidine, respectively, its oral bioavailability is low and variable; due mainly to its poor aqueous solubility. The purpose of this study was to improve famotidine dissolution through its formulation into liquisolid systems and then to investigate the in vitro and in vivo performance of the prepared liquisolid tablets. The new mathematical model was utilized to formulate various liquisolid powder systems. Both DSC and XRD suggested loss of famotidine crystallinity upon liquisolid formulation which was further confirmed by SEM indicating that even though the drug existed in a solid dosage form, it is held within the powder substrate in a solubilized, almost molecularly dispersed state, which contributed to the enhanced drug dissolution properties. All the tested liquisolid tablet formulations showed higher drug dissolution rates (DR) than the conventional, directly compressed tables. In addition, the selected optimal formula released 78.36% of its content during the first 10 min which is 39% higher than that of the directly compressed tablets. Further, the bioavailability study indicated that the prepared optimal liquisolid formula did not differ significantly from the marketed famotidine tablets concerning Cmax, tmax, and AUC(0-8) at P<0.05.  相似文献   

13.
目的 评价单面带刻痕的格列喹酮片的分剂量药学特性。方法 分别采用切药器和手工对自研品和参比制剂进行分割,以分割前后质量损失为评价指标,考察自研品和参比制剂的可分割性;取在硬度上限(8 kg)和下限(4 kg)处的自研格列喹酮片分别用切药器分割后,考察分割质量损失;按照《中国药典》2020年版片剂脆碎度检查法研究分割后的片剂脆碎度;参考《欧洲药典》,随机取30片,分割后检测单一半片占半片平均片质量百分比;高效液相色谱法测定格列喹酮整片、半片在pH 8.5磷酸盐缓冲液中的溶出曲线;参照《中国药典》含量均匀度检查法(通则0941),对切药器分割后的30片自研品进行含量均匀度测定。结果 质量损失结果表明手工分割和切药器分割无显著性差异;硬度上限与下限时片剂分割后的脆碎度和质量损失均符合要求;分割后片剂质量差异、脆碎度和含量均匀度均符合药典要求;自研品与参比制剂的半片溶出行为一致;与整片溶出量相比,分割后的自研品60 min溶出量为51.46%,参比制剂为49.12%。结论 自研品和参比制剂分割后的药学特性相同。  相似文献   

14.
The aim of the work was to improve the dissolution properties of the practically insoluble antiepileptic drug, Carbamazepine (CBZ) by adopting the liquisolid compaction technique. Reported liquid load factors, and excipient ratios were used to calculate the required amounts of excipients necessary to prepare the compacts or tablets according to a mathematical model. Avicel PH 102, and Aerosil 200 were used as the carrier and the coating materials, respectively, and explotab was used as disintegrant to prepare four tablet formulae, out of which formula 1 was successfully compressed into tablets. The dissolution patterns of liquisolid CBZ tablets, carried out according to the USP, were comparable to those of Tegretol®. The protection of male albino mice against the convulsion, induced by electroshock, was lower in case of liquisolid tablets compared to Tegretol® suspension and tablets probably due to the precipitation of CBZ in the silica pores resulting from its high dose.  相似文献   

15.
The objective of this study is to explore and investigate the reservoir mini tablets approach to control the release of Galantamine Hydrobromide in comparison to desired release profile to the Innovator formulation Razadyne® ER capsules as disclosed in US Patent 7,160,559 which is granted to Janseen Pharmaceutica NV. The core mini tablets were prepared using the direct compression and wet granulation methods. These core mini tablets were further coated with Galantamine Hydrobromide in two different portions; 70% as controlled release and 30% as immediate release and then filled in empty hard gelatin capsule shells. The dissolution profiles of each formulation were compared to those of Razadyne® ER capsules and the mean dissolution time (MDT), dissolution efficiency (DE%) and dissolution similarity (f2 factor) were calculated. It was observed that core formulation plays an important role in controlling the drug release as well as maintaining pH independent drug release profile. The release mechanism of GAH from reservoir mini tablet formulation follows Higuchi and first order. These results imply that controlled release reservoir mini tablets which further filled into empty hard gelatin capsule shells can be a suitable method to formulate controlled release Galantamine hydrobromide.  相似文献   

16.
Febuxostat (FXS) is a potent antigout drug with poor water solubility and relative high first-pass effect leading to moderate oral bioavailability (<49%). This study aimed to increase FXS solubility and bioavailability by optimizing sublingual fast-dissolving films (SFs) containing a selected FXS self-nano-emulsifying system (s-SNES) previously prepared by our team. The s-SNES was loaded into SFs by solvent casting technique. A full factorial design (32) was applied to study the effects of polymer and plasticizer types on mechanical characteristics and the dissolution profile of FXS from the SFs. Numerical optimization was performed to select the SF having highest desirability according to predetermined characteristics. The optimized SF (O-SF) contained 1 g of s-SNES, polyvinylpyrrolidone K30 (6%w/v), polyethylene glycol 300 (20%w/w of polymer wt.), and Avicel PH101 (0.5%w/v). O-SF showed good permeation of FXS through sheep sublingual tissue. Storage of O-SF for three months showed no significant change in the FXS dissolution profile. In-vivo performance of O-SF in rabbits was compared to that of oral marketed tablets (Staturic® 80 mg). A cross-over design was applied and pharmacokinetic parameters were calculated after ensuring absence of sequence effect. Statistical analysis revealed better performance for O-SF with significantly higher Cmax, AUC0–24, AUC0–∞, apparent t1/2 together with lower tmax, and apparent kel than marketed tablets. Relative bioavailability of O-SF compared to the marketed tablet was found to be 240.6%. This confirms the achievement of the study aims of improving dissolution rate and bioavailability of FXS using a patient-wise convenient formula.  相似文献   

17.
目的建立盐酸二甲双胍片溶出度测定方法,并分别比较250 mg及500 mg 2种规格国产盐酸二甲双胍片与国际公认参比制剂的溶出曲线。方法分别以水、0.1 mol·L-1盐酸、pH 4.0及pH 6.8磷酸盐缓冲溶液为溶出介质,采用桨法进行体外溶出度试验。用高效液相-紫外分光光度法(HPLC-UV)测定溶出介质中药物含量,并采用溶出度相似因子(f2值)分别评价国产片(每片250 mg)与日本橙皮书Glycoran(每片250 mg)、国产片(每片500 mg)与欧盟上市Merck SantéS.A.S(每片500 mg)在各pH介质中的相似性。结果每片250 mg的2种制剂在各溶出介质中,15 min内的溶出百分率均>85%。在0.1 mol·L-1盐酸的溶出介质中,国产盐酸二甲双胍片(每片500 mg)与欧盟上市Merck SantéS.A.S(每片500 mg)的溶出曲线f2值为78.5(>50);在水、pH 4.0及pH 6.8磷酸盐缓冲溶液的溶出介质中,2种制剂的溶出曲线f2值均<50。结论 2种规格为每片250 mg的盐酸二甲双胍片溶出行为相似。除0.1 mol·L-1的盐酸介质外,2种规格为每片500 mg的盐酸二甲双胍片在各种溶出介质中的溶出行为不相似。  相似文献   

18.
In vitro dissolution profiles of three controlled-release mesalazine formulations were determined at pH 1.0, 6.0 and 7.5. A closed-column type dissolution apparatus was used. A reproducible gradual dissolution profile was seen for Pentasa® at all pH values. Dissolution starts immediately and is complete after 20 h. Dissolution profiles at pH 1 and pH 7.5 are much alike and dissolution is faster than at pH 6. The behaviour of Asacol® at different pH values corresponds with the expectations: no release at pH 6 and pH 1, fast release at pH 7.5. Dissolution starts after 1 h and is complete after 3 h. Mesalazine release from Salofalk® tablets at pH 7.5 and pH 6.0 starts after 2 and 3 h, respectively, and is complete after 5 and 10 h. However, after a long lag-time (10 h) mesalazine is also released from Salofalksu® tablets at pH 1 and dissolution is complete after 23 h.  相似文献   

19.
The bioavailability of josamycin from a tablet formulation (2 × Josacine® 500 mg tablets) was investigated and compared with the bioavailability of a solution (containing 1 g drug and buffered at pH 4.0) following administration to six healthy human volunteers. Bioavailability profiles for the solution indicated that the drug was inherently rapidly absorbed with a mean Cmax of 1.64±0.67 mg L−1 attained at a mean tmax of 0.39±0.08 h. The AUC0–last was 1.510±0.687 mg h L−1. Bioavailability was significantly lower from the tablets than from the solution. Highly variable serum concentration–time profiles were obtained from the tablets and Cmax values ranged from 0.05 to 0.71 mg L−1 with a tmax range of 0.33–2.0 h. AUC0–last values ranged from 0.03 to 0.95 mg h L−1. Dissolution of josamycin from the tablets was generally unaffected at low pH (pH 1.2–5.0), but, rather, limited predominantly by tablet disintegration. However, dissolution was increasingly limited as the pH increased from 5.0 to 9.0. Besides poor disintegration, the particularly low intrinsic dissolution rate and solubility of josamycin at these pH values is likely to further reduce the dissolution rate. Comparison of the solution and tablet serum concentration–time profiles suggests that the absorption of josamycin from the tablets was dissolution rate limited. This is supported by the in vitro dissolution–pH topogram, which suggests that dissolution will be particularly rate limiting if dissolution of whole or parts of tablets occurs in gastro-intestinal fluid above pH 5.0. © 1998 John Wiley & Sons, Ltd.  相似文献   

20.
This investigation evaluated some new (Preflo®) and existing commercially available (Starch 1500, Star Tab) modified starches as direct compression excipients. Preflo® corn starches (CH-10, CH-20, CH-30) and Preflo® potato starches (P-250, PI-10, PJ-20) were evaluated and compared with respect to their pharmaceutical properties such as particle size, density, flowability, friability, and compression properties. Preflo® starches showed a high bulk density and good flowability. Preflo® corn starches and Star Tab formed harder tablets than Preflo® potato starches and Starch 1500. Data from the Athy-Heckel plots indicated that the Preflo® starches are soft materials and, unlike Starch 1500, undergo plastic deformation. Tablets containing acetaminophen were also compressed with the starches and disintegration and dissolution studies were conducted. Starch 1500 tablets disintegrated in 3.5 min, whereas none of the Preflo® starch tablets disintegrated in 30 min. While complete acetaminophen release occurred in 25 min from Starch 1500 tablets, the drug dissolution time from Preflo® starch tablets varied from 4 to 12 hr, indicating a potential use for some of these starches in solid oral modified-release dosage forms.  相似文献   

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