共查询到20条相似文献,搜索用时 31 毫秒
1.
Changhai Qu Lingling Zhang Xueying Du Xiaoyan Zhang Jiao Zheng Yunfang Zhao 《Drug development and industrial pharmacy》2018,44(5):707-712
Objective: To prepare a new nanosystem of usnic acid (UA) with higher solid content and higher bioavailability.Methods: Usnic acid nanocrystal suspensions were prepared by the wet milling method, and then the particle size distributions and zeta potential were determined with the Nano ZS90 laser diffraction particle size analyzer. The particles morphology of UA-NCS were observed by scanning electron microscopy method. In addition, solubility and dissolution of UA-NCS in water and phosphate buffer solution were determined in vitro, analyzed by the HPLC method, and then the cellular uptake and pharmacokinetic were carried out on the Caco-2 cells and rats, analyzed by the UPLC-MS/MS method.Results: Particle size distributions and zeta potential of the UA nanocrystal suspension were 268.7?±?4.0?nm and –23.1?±?0.7?mV, respectively. About the dissolution rate of UA, nanosuspension were significantly faster and higher than common suspension in water and phosphate buffer. And in cellular uptake experiments, the ratio of the maximum amount of drug in unit protein of UA nanosuspension to common suspension was 2.8 times. In rats, oral absorption of nanocrystal UA were superior to the ordinary groups, with the 348% of the maximum concentration and 181% of the AUC after the same dosage administration.Conclusion: The wet-milling technique was suitable for the preparation of UA nanocrystal suspension, and a new nanosystem of UA with higher solid content and higher bioavailability was achieved. 相似文献
2.
《Drug development and industrial pharmacy》2013,39(9):1054-1063
Objective: The purpose of this study was to investigate the dissolution and oral bioavailability of an immediate-release tablet involving wet grinding of a poorly water-soluble drug, fenofibrate. Methods: The milled suspension was prepared using a Basket Dispersing Mill in the presence of a hydrophilic polymer solution and then granulated with common excipients, and compressed into an immediate-release tablet with blank microcrystalline cellulose granules. Results: Compared with unmilled tablets (56% within 30 minutes), the dissolution of wet-milled tablets (about 98% in 30 minutes) was markedly enhanced. No significant decrease in the dissolution rate (96% in 30 minutes) of the wet-milled tablet was observed after 3 months under 40°C and 75% relative humidity storage. In addition, the oral bioavailability of the wet-milled tablets (test) and Lipanthyl® supra-bioavailability tablets (reference) was determined in beagle dogs after a single dose (160 mg fenofibrate) in a randomized crossover, own-control study. The results suggested that both the area under the plasma concentration–time curve (AUC(0?t) = 46.83 ± 11.09 μg/mL h) and the mean peak concentration of the test (Cmax = 4.63 ± 1.71 μg/mL) were higher than the reference (AUC(0?t) = 35.12 ± 10.97 μg/mL h, Cmax = 2.11 ± 0.08 μg/mL). The relative bioavailability of the wet-milled tablet was approximately 1.3-fold higher. Furthermore, the apparent rate of absorption of fenofibrate from the wet-milled tablet (Tmax = 2.63 hours) was faster than that from Lipanthyl® (Tmax = 3.75 hours). Conclusion: These results indicated that the dissolution and the bioavailability of fenofibrate were significantly enhanced by wet-grinding process. So, this shows that wet grinding is a powerful technique to improve the bioavailability for poorly water-soluble drugs, especially for Biopharmaceutics Classification System Class II compounds. 相似文献
3.
Scott M. Krull Zhelun Ma Meng Li Rajesh N. Davé 《Drug development and industrial pharmacy》2016,42(7):1073-1085
The aim of this study is to assess pullulan as a novel steric stabilizer during the wet-stirred media milling (WSMM) of griseofulvin, a model poorly water-soluble drug, and as a film-former in the preparation of strip films via casting–drying the wet-milled drug suspensions for dissolution and bioavailability enhancement. To this end, pullulan films, with xanthan gum (XG) as thickening agent and glycerin as plasticizer, were loaded with griseofulvin nanoparticles prepared by WSMM using pullulan in combination with sodium dodecyl sulfate (SDS) as an ionic stabilizer. The effects of drug loading and milling time on the particle size and suspension stability were investigated, as well as XG concentration and casting thickness on film properties and dissolution rate. The nanosuspensions prepared with pullulan–SDS combination were relatively stable over 7 days; hence, this combination was used for the film preparation. All pullulan-based strip films exhibited excellent content uniformity (most?<3% RSD) despite containing only 0.3–1.3?mg drug, which was ensured by the use of precursor suspensions with?>5000 cP viscosity. USP IV dissolution tests revealed fast/immediate drug release (t80?30?min) from films?<120?μm thick. Thinner films, films with lower XG loading, or smaller drug particles led to faster drug dissolution, while drug loading had no discernible effect. Overall, these results suggest that pullulan may serve as an acceptable stabilizer for media milling in combination with surfactant as well as a fast-dissolving film former for the fast release of poorly water-soluble drug nanoparticles. 相似文献
4.
Khaled El-Refai Mahmoud H. Teaima Mohamed A. El-Nabarawi 《Drug development and industrial pharmacy》2018,44(6):988-1000
Erectile dysfunction (ED) is the most important disorder after premature ejaculation for sexual activity in men. Vardenafil hydrochloride (VH) is an oral therapy for the treatment of erectile dysfunction. VH oral disintegrating tablets (ODTs) have been prepared by freeze drying technique to improve its dissolution profile and the overall clinical performance. Dapoxetine hydrochloride (DH) was added to the best three formulae of the prepared VH ODTs to treat premature ejaculation. All the ODTs formulae were evaluated for weight variation, friability, drug content, in vitro disintegration time, wetting time, and the dissolution study. Gelatin as a matrix former with N-methylpyrrolidone as a solubilizer in VH/DH ODTs improved the dissolution rate and extent of release of VH and DH with 100% of drug being dissolved after 15?min. In vivo study results from six healthy male volunteers showed shorter Tmax of VH from VH/DH ODT of 0.583?±?0.129?h and shorter Tmax of DH from VH/DH ODT of 0.625?±?0.137?h and showed AUC0–12 of VH from VH/DH ODT of 39.234?±?10.932?ng/ml?h1 and AUC0–12 of DH from VH/DH ODT of 531.681?±?129.544?ng/ml?h1, with relative bioavailability values of 100.9 and 85%, respectively, compared to (Levitra®) and (Priligy®). 相似文献
5.
Jingjing Wang Xueyi Ye Shiyuan Lin Hanfu Liu Yin Qiang Hui Chen 《Drug development and industrial pharmacy》2018,44(11):1725-1732
Naringin (NA) is one of typical flavanone glycosides widely distributed in nature and possesses several biological activities including antioxidant, anti-inflammatory, and antiapoptotic. The aim of this study was to develop solid dispersion (SD) and to improve the dissolution rate and oral bioavailability of NA. NA–SD was prepared by the traditional preparation methods using PEG6000, F68, or PVP K30 as carrier at different drug to carrier ratios. According to the results of solubility and in vitro dissolution test, the NA–PEG6000 (1:3) SD was considered as an optimal formulation to characterize by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry and powder X-ray diffraction. Furthermore, oral bioavailabilities of NA–PEG6000 (1:3) SD and NA–suspension with the same dosage were investigated in SD rats. The results confirmed the formation of SD and the pharmacokinetic parameters of NA–PEG6000 (1:3) SD (Cmax?=?0.645?±?0.262?µg/ml, AUC0–t?=?0.471?±?0.084?µg/ml?h) were higher than that of NA–suspension (Cmax?=?0.328?±?0.183?µg/ml, AUC0–t =?0.361?±?0.093?µg/ml?h). Based on the results, the SD is considered as a promising approach to enhance the dissolution rate and oral bioavailability of NA. 相似文献
6.
Soad A. Mohamad Hamdy Abdelkader Mahmoud Elrehany 《Drug development and industrial pharmacy》2019,45(2):244-251
Attempting to prepare a convenient bioavailable formulation of vitamin B12 (cyanocobalamin), 17 tablet formulations were prepared by direct compression. Different concentrations of hydroxypropyl methyl cellulose (HPMC), carbopol 971p (CP971p), and chitosan (Cs) were used. The tablets were characterized for thickness, weight, drug content, hardness, friability, surface pH, in vitro drug release, and mucoadhesion. Kinetic analysis of the release data was conducted. Vitamin B12 bioavailability from the optimized formulations was studied on rabbits by the aid of enzyme-linked immunosorbent assay. Neurotone® I.M. injection was used for comparison. HPMC (F1-F4), CP971p (F5-F8), and HPMC/CP971p (F12-F15)-based formulations showed acceptable mechanical properties. The formulated tablets showed maximum swelling indices of 232?±?0.13. The surface pH values ranged from 5.3?±?0.03 to 6.6?±?0.02. Bioadhesive force ranged from 66?±?0.6 to 150?±?0.5?mN. Results showed that CP971p-based tablets had superior in vitro drug release, mechanical, and mucoadhesive properties. In vitro release date of selected formulations were fitted well to Peppas model. HPMC/CP971p-based formulations showed bioavailability up to 2.7-folds that of Neurotone® I.M. injection. 相似文献
7.
《Drug development and industrial pharmacy》2013,39(11):1344-1353
Objective: The objective of this study is to investigate the wet-milled-drug layering process which could significantly improve the dissolution rate and oral bioavailability of fenofibrate pellets.Methods: Fenofibrate was milled with HPMC-E5 to prepare a uniform suspension in the micrometer and nanometer range, and this suspension was then layered on to sugar spheres to form the pellets (F1, F2).Results: The particle size was significantly reduced (from 1000 µm to 1–10 µm and 400?nm) but the fenofibrate in suspension retained its crystallinity from the results of DSC and PXRD investigations. The dissolution rate of F1-F2 and Antara® capsules was 55.47 %, 61.27 % and 58.43 %, respectively, in 0.01?mol/L SDS solution over 60?min. In addition, F1, F2, and Antara® capsules were given orally to 6 beagle dogs to determine the bioavailability. The Cmax of F1, F2 (8.21?±?2.55 and 9.33?±?2.37 μg/mL)and the AUC(0?t) of F1, F2 (152.46?±?78.89 and 172.17?±?67.58 μg/mL·h)were higher than those of Antara® (6.02?±?3.34 μg/mL and 89.82?±?46.46 μg/mL·h) and, F1, F2 reached their Cmax earlier than Antara® (F1: 2.0?±?1.1?h; F2: 1.8?±?1.2?h; Antara®: 6.0?±?8.9?h).Conclusion: These results show that the wet-milled-drug layering technique is a powerful method to improve the dissolution rate and the bioavailability of fenofibrate. 相似文献
8.
Vijaykumar Nekkanti Natarajan Venkatesan Zhijun Wang Guru V. Betageri 《Drug development and industrial pharmacy》2015,41(12):2077-2088
AbstractThe objective of our investigational work was to develop a proliposomal formulation to improve the oral bioavailability of valsartan. Proliposomes were formulated by thin film hydration technique using different ratios of phospholipids:drug:cholesterol. The prepared proliposomes were evaluated for vesicle size, encapsulation efficiency, morphological properties, in vitro drug release, in vitro permeability and in vivo pharmacokinetics. In vitro drug-release studies were performed in simulated gastric fluid (pH 1.2) and purified water using dialysis bag method. In vitro drug permeation was studied using parallel artificial membrane permeation assay (PAMPA), Caco-2 monolayer and everted rat intestinal perfusion techniques. In vivo pharmacokinetic studies were conducted in male Sprague Dawley (SD) rats. Among the proliposomal formulations, F-V was found to have the highest encapsulation efficiency of 95.6?±?2.9% with a vesicle size of 364.1?±?14.9?nm. The in vitro dissolution studies indicated an improved drug release from proliposomal formulation, F-V in comparison to pure drug suspension in both, purified water and pH 1.2 dissolution media after 12?h. Permeability across PAMPA, Caco-2 cell and everted rat intestinal perfusion studies were higher with F-V formulation as compared to pure drug. Following single oral administration of F-V formulation, a relative bioavailability of 202.36% was achieved as compared to pure valsartan. 相似文献
9.
《Drug development and industrial pharmacy》2013,39(5):557-570
Rapid flocculation of nanoparticle dispersions of a poorly water soluble drug, itraconazole (Itz), was utilized to produce amorphous powders with desirable dissolution properties for high bioavailability in rats. Antisolvent precipitation (AP) was utilized to form Itz nanodispersions with high drug loadings stabilized with hydroxypropylmethylcellulose (HPMC) or the pH-sensitive Eudragit® L100-55 (EL10055). The HPMC dispersions were flocculated by desolvating the polymer through the addition of a divalent salt, and the enteric EL10055 by reducing the pH. The formation of open flocs by diffusion limited aggregation facilitated redispersion of the flocs at pH 6.8. Upon redispersion of the flocculated nanoparticles at pH 6.8, the particle size was modestly larger than the original size, on the order of 1 μm. High in vitro supersaturation (AUC) of the flocculated nanoparticle dispersions was observed in micellar media at pH 6.8, after 2 hours initial exposure at pH 1.2 to simulate the stomach, relative to the AUC for a commercially available Itz formulation, Sporanox. Greater in vivo bioavailability in rats was correlated directly to the higher in vitro AUC at pH 6.8 with micelles during the pH shift experiment for the flocculated nanoparticle dispersions relative to Sporanox. The ability to generate and sustain high supersaturation in micellar media at pH 6.8, as shown with the in vitro pH shift dissolution test, is beneficial for increasing bioavailability of Itz by oral delivery. 相似文献
10.
Mohamed F. Zidan Mohsen I. Afouna Elsherbeny A. Ibrahim 《Drug development and industrial pharmacy》2018,44(8):1243-1253
The aim of this study was to explore the feasibility of complexing the poorly water-soluble drug atorvastatin calcium (AC) with β-cyclodextrin (β-CD) based nanosponges (NS), which offer advantages of improving dissolution rate and eventually oral bioavailability. Blank NS were fabricated at first by reacting β-CD with the cross-linker carbonyldiimidazole at different molar ratios (1:2, 1:4, and 1:8), then NS of highest solubilization extent for AC were complexed with AC. AC loaded NS (AC-NS) were characterized for various physicochemical properties. Pharmacokinetic, pharmacodynamics and histological finding of AC-NS were performed in rats. The prepared AC-NS showed particles size ranged from 408.7?±?12.9 to 423?±?15.9?nm while zeta potential values varied from ?21.7?±?0.90 to ?22.7?±?0.85?mV. The loading capacity varied from 17.9?±?1.21 to 34.1?±?1.16%. DSC, FT–IR, and PXRD studies confirmed the complexation of AC with NS and amorphous state of the drug in the complex. AC-NS displayed a biphasic release pattern with increase in the dissolution rate of AC as compared to plain AC. Oral administration of AC-NS (1:4 w/w, drug: NS) to rats led to 2.13-folds increase in the bioavailability as compared to AC suspension. Pharmacodynamics studies in rats with fatty liver revealed significant reduction (p?.05) in total cholesterol, triglyceride, LDL-C and increased level of beneficial HDL-C along with improvement in the associated liver steatosis as confirmed through photomicrographs of liver sections. In this study, we confirmed that complexation of AC with NS would be a viable approach for improving oral bioavailability and in vivo performance of AC. 相似文献
11.
Bhaskar Daravath Sateesh Kumar Vemula 《Drug development and industrial pharmacy》2015,41(8):1254-1262
Context: Development of solid dispersions is to improve the therapeutic efficacy by increasing the drug solubility, dissolution rate, bioavailability as well as to attain rapid onset of action.Objective: The present research deals with the development of solid dispersions of flurbiprofen which is poorly water soluble to improve the solubility and dissolution rate using gelucires.Materials and methods: In this study, solid dispersions were prepared following solvent evaporation method using gelucire 44/14 and gelucire 50/13 as carriers in different ratios. Then the formulations were evaluated for different physical parameters, solubility studies, DSC, FTIR studies and in vitro dissolution studies to select the best formulation that shows rapid dissolution rate and finally subjected to pharmacokinetic studies.Results and discussion: From the in vitro dissolution study, formulation F3 showed the better improvement in solubility and dissolution rate. From the pharmacokinetic evaluation, the control tablets produced peak plasma concentration (Cmax) of 9140.84?±?614.36?ng/ml at 3?h Tmax and solid dispersion tablets showed Cmax?=?11?445.46?±?149.23?ng/ml at 2?h Tmax. The area under the curve for the control and solid dispersion tablets was 31?495.16?±?619.92 and 43?126.52?±?688.89?ng h/ml and the mean resident time was 3.99 and 3.68?h, respectively.Conclusion: From the above results, it is concluded that the formulation of gelucire 44/14 solid dispersions is able to improve the solubility, dissolution rate as well as the absorption rate of flurbiprofen than pure form of drug. 相似文献
12.
Shuangshuang Song Baocheng Tian Fen Chen Wenji Zhang Yusheng Pan Qiang Zhang 《Drug development and industrial pharmacy》2015,41(1):51-62
Objective: The objectives of this study were, first, to develop a free-flowing and stable proniosome formulation for poorly water-soluble drugs such as vinpocetine; and second, to estimate its bioavailability as oral drug delivery system.Methods: The proniosomes consisting of span60, cholesterol, sorbitol and vinpocetine were prepared by a novel approach. After the proniosomes were contacted with water, the suspension of vinpocetine-loaded niosomes formed automatically. The proniosomes and reconstituted niosomes were evaluated for their physicochemical characteristics, in vitro drug dissolution and release, integrity and stability at different GI tract pH conditions, in situ single-pass intestinal perfusion and in vivo bioavailability.Results: The proniosome powder exhibited excellent flowability. The reconstituted niosomes with high drug entrapment efficiency (89.67?±?3.28%) showed spherical morphology with smooth surface under transmission electron microscope (TEM). X-ray diffraction (XRD) indicated that the drug was in an amorphous or molecular state in proniosome powder. In vitro dissolution and release study, proniosomes did enhance the dissolution and release rate compared to vinpocetine suspension in phosphate buffer solution (pH 7.2). Proniosome-derived niosomes could keep their integrity and stability at different GI tract pH conditions. The in situ single-pass intestinal perfusion indicated that encapsulation of vinpocetine into niosomes could largely improved the absorption of vinpocetine. The AUC(0?∞) of F2 and F3 was about 4.0- and 4.9-fold higher than that of the vinpocetine suspension, respectively. The results demonstrated the proniosomes indeed remarkably enhanced the oral bioavailability of vinpocetine.Conclusion: This study suggested the potential of proniosomes as stable precursors for the immediate preparation of niosome carrier systems. 相似文献
13.
Eman Abd-Elrasheed Manal M. EL-Ashmoony Salwa Salah 《Drug development and industrial pharmacy》2018,44(5):741-749
Intranasal zaleplon solid dispersion was formulated to enhance the solubility, bioavailability and deliver an effective therapy. Zaleplon belongs to Class II drugs, and undergoes extensive first-pass metabolism after oral absorption exhibiting 30% bioavailability. A 23 full-factorial design was chosen for the investigation of solid dispersion formulations. The effects of different variables include drug to carrier ratio (1:1 and 1:2), carrier type (polyethylene glycol 4000 and poloxamer 407), and preparation method (solvent evaporation and freeze drying) on different dissolution parameters were studied. The dependent variables determined from the in vitro characterization and their constraints were set as follows: minimum mean dissolution time, maximum dissolution efficiency and maximum percentage release. Numerical optimization was performed according to the constraints set based on the utilization of desirability functions. Differential scanning calorimetry, infrared spectroscopy, X-ray diffraction and scanning electron microscopy were performed. Ex vivo estimation of nasal cytotoxicity and assessment of the γ-aminobutyric acid level in plasma and brain 1?h after nasal SD administration in rabbits compared to the oral market product were conducted. The selected ZP-SD, with a desirability 0.9, composed of poloxamer 407 at drug to carrier ratio 1:2 successfully enhanced the bioavailability showing 44% increase in GABA concentration than the marketed tablets. 相似文献
14.
Hong-Xing Fu Hui Li Lan-Lan Wu Ying-Zheng Zhao Yan-Yan Xu Yan-Lin Zhu 《Drug development and industrial pharmacy》2014,40(11):1523-1529
Ca-alginate-poly-l-lysine-alginate (APA-Ca) and Ba-alginate-poly-l-lysine-alginate (APA-Ba) microcapsules were prepared and their thickness and surface were examined by light microscopy and scanning electron microscopy. Specifically, light microscopy with frozen section was used to visualize and quantify the thickness of APA membrane, and monitor temporal changes in the thickness of microcapsules during a month long culture in vitro. The section graph of APA microcapsule represents the accurate measurement of layer thickness of APA-Ca with diameter 900?±?100 and 500?±?100?μm at 6.01?±?1.02 and 9.54?±?2.42?μm (p?0.05), and layer thickness of APA-Ba with diameter 900?±?100 and 500?±?100?μm at 5.47?±?0.90 and 8.21?±?1.97?μm (p?0.05), regardless of the alginate composition used to generate the microcapsules. The microcapsule was stable during the culture for 30 days in vitro. Field emission scanning electron microscopy with freeze drying method was used to detect the surface and thickness of dried microcapsules. From the results, the outer surface of APA-Ca and APA-Ba membrane were smooth and dense, the film thickness of the APA-Ca was about 450–690?nm, while the APA-Ba was approximately 335?nm. In vivo experiment, little significant difference was seen in the change of film thickness of microcapsules in intrapertioneal site for 30 days after transplantation (p?>?0.05), except that the recovery of APA-Ba was higher than the APA-Ca microcapsules. The paper showed an easy method to prepare APA-Ca and APA-Ba, and examine their thickness and surface, which could be utilized to study other types of microcapsules. 相似文献
15.
Dong Hoon Oh Yi-Dong Yan Dong Wuk Kim Jong Oh Kim Chul Soon Yong 《Drug development and industrial pharmacy》2014,40(2):172-177
Objective: A novel flurbiprofen-loaded nanoemulsion which gave uniform emulsion droplets with a narrow size distribution was previously reported to be prepared using membrane emulsification method. The purpose of this study is to develop a novel flurbiprofen-loaded nanoparticle with a narrow size distribution and improved bioavailability.Method: The nanoparticle was prepared by solidifying nanoemulsion using sucrose as a carrier via spray drying method. Its physicochemical properties were investigated using SEM, DSC and PXRD. Furthermore, dissolution and bioavailability in rats were evaluated compared to a flurbiprofen-loaded commercial product.Results: The flurbiprofen-loaded nanoparticles with flurbiprofen/sucrose/surfactant mixture (1/20/2, weight ratio) gave good solidification and no stickiness. They associated with about 70?000-fold improved drug solubility and had a mean size of about 300 nm with a narrow size distribution. Flurbiprofen was present in a changed amorphous state in these nanoparticles. Moreover, the nanoparticles gave significantly shorter Tmax, and higher AUC and Cmax of the drug compared to the commercial product (p?0.05). In particular, they showed about nine-fold higher AUC of the drug than did the commercial productConclusion: These flurbiprofen-loaded nanoparticles prepared with sucrose by the membrane emulsification and spray drying method would be a potential candidate for orally delivering poorly water-soluble flurbiprofen with enhanced bioavailability. 相似文献
16.
《Drug development and industrial pharmacy》2013,39(11):1381-1389
Purpose: Pranlukast, one of the potential therapeutic tools in the treatment of asthma, has limited clinical applications due to its poor water solubility. The study is aimed to provide a platform for better utilizing pranlukast with enhancement of the dissolution rate and, thus, the oral bioavailability of pranluka’st by preparing nanosuspensions through high-pressure homogenization method.Method: Poloxamer407 and PEG200 were chosen as stabilizer and surfactant. The formulation was investigated systematically with the dissolution tests as predominant method. Nanosuspensions were prepared by programmed high-pressure homogenization method. The product was characterized by particle size analysis, TEM and XRD are evaluated by in vitro dissolution tests and in vivo absorption examination. In addition, nanosuspensions with only pranlukast were prepared and compared with formulated nanosuspensions.Results: The optimal values of formulation were 0.5% (w/v) pranlukast with 0.375% (w/v) Poloxamer407, 0.375% (w/v) PEG200 and the screened programming homogenizing procedure parameters were 680 bar for the first 15 circles, 1048 bar for the next 9 circles and 1500 bar for the last 9 circles. Nanosuspensions of 318.2?±?7.3?nm, ?29.3?±?0.8 mV were obtained. The XRD analysis indicated no change of crystalline occurred in the process of homogenization. The in vitro dissolution behavior of nanosuspensions exhibited complete release in 30?min with a remarkable fast dissolution rate. The in vivo bioavailability of formulated pranlukast nanosuspensions demonstrated its enhancement of fast onset of therapeutic drug effects with 4.38-fold improved compared to that of raw crystals.Conclusion: The study provides a feasible, practical thinking of industry development in the clinical use of pranlukast. 相似文献
17.
Sunny Shah Romik Patel Moinuddin Soniwala Jayant Chavda 《Drug development and industrial pharmacy》2015,41(11):1835-1846
The present work is aimed to develop and optimize pulsatile delivery during dissolution of an improved formulation of valsartan to coordinate the drug release with circadian rhythm. Preliminary studies suggested that β cyclodextrin could improve the solubility of valsartan and showed AL type solubility curve. A 1:1 stoichiometric ratio of valsartan to β cyclodextrin was revealed from phase solubility studies and Job’s plot. The prepared complex showed significantly better dissolution efficiency (p?<?0.05) compared to pure drug, which could be due to the formation of inclusion complex as revealed from FTIR and DSC studies. Continuous dissolution-absorption studies revealed that absorption of drug from valsartan β cyclodextrin complex was significantly higher (p?0.05) compared to pure drug, in second part press-coated tablets of valsartan β cyclodextrin complex were subsequently prepared and application of the Plackett–Burman screening design revealed that HPMC K4M and EC showed significant effect on lag time. A 32 full factorial design was used to measure the response of HPMC K4M and EC on lag time and time taken for 90% drug release (T90). The optimized batch prepared according to the levels obtained from the desirability function had a lag time of 6?h and consisted of HPMC K4M:ethylcellulose in a 1:1.5 ratio with 180?mg of coating and revealed a close agreement between observed and predicted value (R2?=?0.9694). 相似文献
18.
Lei Wang Qing Luo Tongyuan Lin Rui Li Tingting Zhu Kai Zhou 《Drug development and industrial pharmacy》2015,41(7):1204-1212
With the aim to develop a lipid nanoparticle for biochanin A (BCA) by emulsion-evaporation and low temperature-solidification technique. The results revealed that BCA–PEG–NLC not only have small mean particle (148.5?±?2.88?nm) with narrow polydispersity index (PI) (0.153?±?0.01), encapsulation capacity (99.62?±?0.06%), payload (9.06?±?0.01%), zeta potential (?19.83?±?1.19?mV), but also slower release rate compared with BCA suspension over 48?h by the dialysis method (n=3). The crystallinity of lipid matrix within BCA–PEG–NLC was evaluated by differential scanning calorimetry (DSC) which verified the BCA successfully into the nanoparticles. Particularly, in pharmacokinetic, the BCA–PEG–NLC of Cmax values and AUC (area under curve) was higher than BCA suspension (approximately 15.8 and 2.9 times, respectively), meanwhile, the mean residence time (MRT) was significantly longer. Furthermore, in vitro cytotoxicity BCA–PEG–NLC showed higher cytotoxicity against MCF-7 cell line compared with BCA suspension. This study suggested that PEG–NLC is a novel anti-cancer nanoparticle, which could provide attractive treatment for a wide variety of tumors and improved the oral bioavailability of poorly water-soluble drug. 相似文献
19.
Weiqin Wang Changchang Cui Mengying Li 《Drug development and industrial pharmacy》2017,43(7):1178-1185
Novel solid dispersions of oleanolic acid-polyvinylpolypyrrolidone (OLA-PVPP SDs) were designed and prepared to improve the apparent solubility of drug, as well as to improve the stability, fluidity and compressibility of SDs. Disintegrable OLA-PVPP SDs were then evaluated both in vitro and in vivo. DSC, XRD, IR and SEM analysis proved the formation of OLA-PVPP SD and its amorphous state. The results of fluidity study, moisture absorption test and stability test showed that OLA-PVPP SD with good fluidity and qualified stability was successfully obtained. Meanwhile excellent dissolution rate was achieved for in vitro studies; dissolution test showed that ~50–75% of OLA was dissolved from SDs within the first 10?min, which is about 10–15 times of free OLA. In vivo study indicated that the formation of solid dispersion could largely improve the absorption of OLA, resulting in a much shorter Tmax (p?.05) and higher Cmax (p?.01) than those of free drug. The AUC0→∞ of OLA-PVPP SDs (1:6) were 155.4?±?37.24?h·ng/mL compared to the 103.11?±?26.69?h·ng/mL and 94.92?±?13.05?h·ng/mL of OLA-PVPP physical mixture (1:6) and free OLA, respectively. These proved PVPP could be a promising carrier of solid dispersions and was industrially feasible alternative carrier in the manufacture of solid dispersions. 相似文献
20.
《Drug development and industrial pharmacy》2013,39(2):402-412
Context: Along with other options, solid dispersions prepared by spray drying offer the possibility of formulating poorly soluble drugs in a rapidly dissolving format. As a wide range of potential excipients and solvents is available for spray drying, it is usually necessary to carry out a comprehensive array of studies to arrive at an optimal formulation.Objective: To study the influence of formulation parameters such as co-sprayed excipients, solvents and packaging on the manufacture, in vitro performance and stability of spray-dried oral drug products using fenofibrate as a model drug.Materials and methods: Solid dispersions of fenofibrate with different amorphous polymers were manufactured from two solvent systems by spray drying. These were characterized in terms of physicochemical properties, crystalline content and dissolution behavior in biorelevant media upon production and after storage in two packaging systems (Glass and Activ-Vials?).Results and discussion: Spray drying the same formulation from two different solvents led to different physicochemical properties, dissolution behavior and long-term stability. The dissolution behavior and long-term stability also varied significantly among excipients. The viscosity of the polymer and the packaging material proved to be important to the long-term stability.Conclusion: For spray-dried products containing fenofibrate, the excipients were ranked according to dissolution and stability performance as follows: PVP derivatives >> HPMC 2910/15, HPMCAS-MF, HP-β-CD >> PVP:PVA 2:8. EtOH 96% proved superior to acetone/water for spray drying with polymers. The results were used to propose a general approach to developing spray-dried formulations of poorly soluble drugs. 相似文献