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1.
The purpose of this study was to investigate the formulation variables influencing the drug release from the layered tablets
containing chitosan and xanthan gum as matrix component. Increasing the amount of lactose could diminish pH sensitive release
behavior of these matrix tablets. Effect of formulation variables on drug release from the prepared three-layered matrix tablets
was investigated. The amount of drug loading did not affect the drug release which was influenced by the hydrodynamic force
and the matrix composition. An increase in stirring rate correspondingly increased the release rate. Moreover, incorporation
of soluble diluents in core or barrier could enhance the drug release. Least square fitting the experimental dissolution data
to the mathematical expressions (power law, first order, Higuchi’s and zero order) was carried out to study the drug release
mechanism. Most dissolution profiles of the prepared three-layered tablets provided a better fit to zero order kinetic than
to first order kinetic and Higuchi’s equation. 相似文献
2.
The aim of this study was to investigate the influence of polymer level and type of some hydrophobic polymers, including hydrogenated
castor oil (HCO); Eudragit RS100 (E-RS100); Eudragit L100 (E-L100), and some fillers namely mannitol [soluble filler], Dibasic
calcium phosphate dihydrate (Emcompress) and anhydrous dibasic calcium phosphate [insoluble fillers] on the release rate and
mechanism of baclofen from matrix tablets prepared by a hot-melt granulation process (wax tablets) and wet granulation process
(E-RS100 and E-L100 tablets). Statistically significant differences were found among the drug release profile from different
classes of polymeric matrices. Higher polymeric content (40%) in the matrix decreased the release rate of drug because of
increased tortuosity and decreased porosity. At lower polymeric level (20%), the rate and extent of drug release was elevated.
HCO was found to cause the strongest retardation of drug. On the other hand, replacement of Emcompress or anhydrous dibasic
calcium phosphate for mannitol significantly retarded the release rate of baclofen, except for E-L100 (pH-dependent polymer).
Emcompress surface alkalinity and in-situ increase in pH of the matrix microenvironment enhanced the dissolution and erosion of these matrix tablets. The release kinetics
was found to be governed by the type and content of the excipients (polymer or filler). The prepared tablets showed no significant
change in drug release rate when stored at ambient room conditions for 6 months. 相似文献
3.
This study examined the release of carbamazepine (CBZ) from hydrophobic (Compritol 888 ATO) and hydrophilic-hydrophobic matrix combination (Compritol 888 ATO-hydroxpropyl methylcellulose, HPMC). Hydrophobic matrix tablets were prepared by hot fusion technique, while hydrophilic-hydrophobic matrix tablets were prepared by wet granulation technique. The properties of the compressed matrix tablets were determined according to the US Pharmacopoeia. Both matrix formulations displayed a controlled-release profile when compared to the reference formulation (Tegretol CR 200). The bioavailability of CBZ formulations and Tegretol CR 200 were evaluated in beagle dogs. Carbamazepine presented a significant higher bioavailability from matrix tablets containing hydrophilic polymer (HPMC) than that obtained from Tegretol CR200. The average inter-subject plasma concentration variability CV% was the least with tablet containing hydrophilic polymer (HPMC) and was the highest with Tegretol CR 200 (33.8 and 54.1, respectively). Analysis of variance applied to log AUC(0-alpha) and log C(max) showed statistical significant differences among the three formulations (P < 0.05). Plotting the fraction of CBZ released in vitro and fraction absorbed showed a statistically significant relationship (R(2) = 0.935-0.975) for the three matrix tablets examined. 相似文献
4.
The purpose of this research was to design oral controlled release (CR) matrix tablets of zidovudine (AZT) using hydroxypropyl
methylcellulose (HPMC), ethyl cellulose (EC) and carbopol-971P (CP) and to study the effect of various formulation factors
on in vitro drug release. Release studies were carried out using USP type 1 apparatus in 900 ml of dissolution media. Release kinetics
were analyzed using zero-order, Higuchi’s square root and Ritger–Peppas’ empirical equations. Release rate decreased with
increase in polymer proportion and compression force. The release rate was lesser in formulations prepared using CP (20%)
as compared to HPMC (20%) as compared to EC (20%). No significant difference was observed in the effect of pH of dissolution
media on drug release from formulations prepared using HPMC or EC, but significant difference was observed in CP based formulations.
Decrease in agitation speed from 100 to 50 rpm decreased release rate from HPMC and CP formulations but no significant difference
was observed in EC formulations. Mechanism of release was found to be dependent predominantly on diffusion of drug through
the matrix than polymer relaxation incase of HPMC and EC formulations, while polymer relaxation had a dominating influence
on drug release than diffusion incase of CP formulations. Designed CR tablets with pH independent drug release characteristics
and an initial release of 17–25% in first hour and extending the release up to 16–20 h, can overcome the disadvantages associated
with conventional tablets of AZT. 相似文献
5.
Satishkumar P. Jain Pirthi Pal Singh Sharad Javeer Purnima D. Amin 《AAPS PharmSciTech》2010,11(2):936-944
The present paper was focused on exploiting Plackett–Burman design to screen the effect of nine factors—poly (ethylene oxide)
molecular weight (X
1), poly (ethylene oxide) amount (X
2), ethylcellulose amount (X
4), drug solubility (X
5), drug amount (X
6), sodium chloride amount (X
7), citric acid amount (X
8), polyethylene glycol amount (X
9), and glycerin amount (X
11) on the release of drugs from the extended release extrudates, i.e., release rate and release mechanism. The experiments
were carried out according to a nine-factor 12-run statistical model and subjected to an 8-h dissolution study in phosphate
buffer pH 6.8. The significance of the model was indicated by the ANOVA and the residual analysis. Poly (ethylene oxide) amount,
ethylcellulose amount and drug solubility had significant effect on the T90 values whereas poly (ethylene oxide) amount and
ethylcellulose amount had significant effect on the n value. 相似文献
6.
The objectives of this study were to evaluate the physical structure and the release mechanisms of theophylline microspheres
made of Eudragit S 100 polymer as an enteric polymer, combined with a nonerodible polymer, Eudragit RL 100. In the preparation
process, polymer combinations (1:1) were dissolved in an organic solvent mixture composed of acetone and methanol at a specific
ratio containing a theoretical drug loading of approximately 15%. Two microsphere formulations (LS1 and LS2) were prepared
at two different total polymer concentrations (10% in LS1 and 12.7% in LS2). Dissolution studies were carried out using US
Pharmacopeia Dissolution Apparatus II in an acidic medium for 8 h and in an acidic medium (2 h) followed by a slightly basic-buffered
medium for 10 h. Both LS1 and LS2 microsphere formulations produced particles that were spherical in shape and had very narrow
size distributions with one size fraction comprising 70–80% of the yield. Scanning electron microscopy and quantitative Fourier
transform infrared were used for microsphere physical structure evaluation. Except for the absence of drug crystals, photomicrographs
of both LS microspheres after dissolution in pH 1.2 and 7.2 buffer solutions were similar to those before dissolution. Dissolution
results indicated the ability of LS microspheres to minimize drug release during the acid stage. However, in the slightly
basic medium that followed the acidic stage, the drug release was sustained and controlled in its kinetics and data fitted
to Peppas equation indicated a case II transport suggesting that the drug release is mainly through swelling/erosion mechanism. 相似文献
7.
Suprit D. Saoji Sandip C. Atram Pradip W. Dhore Priya S. Deole Nishikant A. Raut Vivek S. Dave 《AAPS PharmSciTech》2015,16(6):1344-1356
The influence of formulation variables, i.e., a hydrophilic polymer (Methocel® E15) and a film-forming polymer (Eudragit® RL 100 and Eudragit® RS 100), on the physicochemical and functional properties of a transdermal film formulation was assessed. Several terpenes were initially evaluated for their drug permeation enhancement effects on the transdermal film formulations. d-Limonene was found to be the most efficient permeation enhancer among the tested terpenes. Transdermal film formulations containing granisetron (GRN) as a model drug, d-limonene as a permeation enhancer, and different ratios of a hydrophilic polymer (Methocel® E15) and a film-forming polymer (Eudragit® RL 100 or Eudragit® RS 100) were prepared. The prepared films were evaluated for their physicochemical properties such as weight variation, thickness, tensile strength, folding endurance, elongation (%), flatness, moisture content, moisture uptake, and the drug content uniformity. The films were also evaluated for the in vitro drug release and ex vivo drug permeation. The increasing ratios of Methocel®:Eudragit® polymers in the formulation linearly and significantly increased the moisture content, moisture uptake, water vapor transmission rate (WVTR), and the transdermal flux of GRN from the film formulations. Increasing levels of Methocel® in the formulations also increased the rate and extent of the GRN release and the GRN permeation from the prepared films.KEY WORDS: film-forming polymers, hydrophilic polymers, permeation enhancers, transdermal films 相似文献
8.
Biki Gupta Bijay Kumar Poudel Shiva Pathak Jin Wook Tak Hee Hyun Lee Jee-Heon Jeong Han-Gon Choi Chul Soon Yong Jong Oh Kim 《AAPS PharmSciTech》2016,17(3):652-662
Imatinib (IMT), an anticancer agent, inhibits receptor tyrosine kinases and is characterized by poor aqueous solubility, extensive first-pass metabolism, and rapid clearance. The aims of the current study are to prepare imatinib-loaded solid lipid nanoparticles (IMT-SLN) and study the effects of associated formulation variables on particle size and drug encapsulation on IMT-SLN using an experimental design. IMT-SLN was optimized by use of a “combo” approach involving Plackett-Burman design (PBD) and Box-Behnken design (BBD). PBD screening resulted in the determination of organic-to-aqueous phase ratio (O/A), drug-to-lipid ratio (D/L), and amount of Tween® 20 (Tw20) as three significant variables for particle size (S z), drug loading (DL), and encapsulation efficiency (EE) of IMT-SLN, which were used for optimization by BBD, yielding an optimized criteria of O/A?=?0.04, D/L?=?0.03, and Tw20?=?2.50%?w/v. The optimized IMT-SLN exhibited monodispersed particles with a size range of 69.0?±?0.9 nm, ζ-potential of ?24.2?±?1.2 mV, and DL and EE of 2.9?±?0.1 and 97.6?±?0.1%?w/w, respectively. Results of in vitro release study showed a sustained release pattern, presumably by diffusion and erosion, with a higher release rate at pH 5.0, compared to pH 7.4. In conclusion, use of the combo experimental design approach enabled clear understanding of the effects of various formulation variables on IMT-SLN and aided in the preparation of a system which exhibited desirable physicochemical and release characteristics. 相似文献
9.
In the present investigation, hydrogenated cottonseed oil (HCSO) was evaluated as a sustained release matrix for a freely
soluble drug, tramadol. Hydrophobic matrix tablets of tramadol, was evaluated by compression of physical mixture of drug and
wax, dispersion of drug in HCSO by hot fusion or solubilisation techniques. The method of preparation of tablet had a significant
effect on drug release with higher release observed from direct compression matrices and slower release from matrix prepared
by dispersion (hot-fused matrices). Influence of addition of hydroxypropylmethyl cellulose, sodium carboxymethyl cellulose,
polyethylene glycol 4000 and surfactants like sodium lauryl sulphate and polysorbate 20 to HCSO matrix on drug release was
investigated. The added excipients exhibited a propensity to enhance drug release from the HCSO matrix. NaCMC was effective
at a lower ratio (<10% w/w) and when incorporated at higher level made HCSO matrix to erode and disintegrate in a short period. 相似文献
10.
The purpose of this research was to develop and evaluate different preparations of sustained delivery systems, using Carbopols
as carriers, in the form of matrices and three-layer tablets with isosorbite mononitrate. Matrix tablets were prepared by
direct compression whereas three-layer tablets were prepared by compressing polymer barrier layers on both sides of the core
containing the drug. The findings of the study indicated that all systems demonstrated sustained release. The properties of
the polymer used and the structure of each formulation appear to considerably affect drug release and its release rate. The
three-layer formulations exhibit lower drug release compared to the matrices. This was due to the fact that the barrier-layers
hindered the penetration of liquid into the core and modified drug dissolution and release. The geometrical characteristics/structure
of the tablets as well as the weight/thickness of the barriers-layers considerably influence the rate of drug release and
the release mechanisms. Kinetic analysis of the data indicated that drug release from matrices was mainly attributed to Fickian
diffusion while three-layer tablets exhibited either anomalous diffusion or erosion/relaxation mechanisms. The advantage of
Carbopol formulations is that a range of release profiles can easily be obtained through variations in tablet structure and
thus Carbopols are appropriate carriers of oral sustained drug delivery systems for soluble drugs such as the isosorbite mononitrate. 相似文献
11.
Huang Jinheng Lin Huaqing Peng Bingxin Huang Qianfeng Shuai Fangzhou Xie Yanxian 《AAPS PharmSciTech》2018,19(5):2144-2154
The aim of this research was to design and evaluate a hydrophilic matrix system for sustained release of glipizide, a weakly acidic poor soluble drug. A combination of inclusion complexation and microenvironmental pH modification techniques was utilized to improve the dissolution and pH-independent release of glipizide. Hydroxypropyl-β-cyclodextrin (HP-β-CD) was used as the complexation agent while sodium citrate and magnesium oxide (MgO) were used as model pH modifiers. The hydrophilic matrix tablets were prepared by powder direct compression and evaluated by in vitro dissolution study respectively in pH 6.8 and pH 1.2 dissolution media. The formulations containing MgO exhibited increased cumulative drug release from less than 40% in the reference formulation to 90% within 24 h in acidic media (pH 1.2). The release profile in acidic media was similar to the alkaline media (pH 6.8) with a similarity factor (f2) of 55.0, suggesting the weakening of the effect of pH on the dissolution efficiency of glipizide. The release profile fitted well into the Higuchi model and the dominant mechanism of drug release was Fickian diffusion while case II transport/polymer relaxation occurred. In conclusion, combining inclusion complexation agents and pH modifiers had improved the dissolution of glipizide as well as achieved the pH-independent release profile. 相似文献
12.
The aim of this study was to microencapsulate caffeine by the emulsion technique, trying to control its release from a medicated chewing gum. Three formulations were prepared using alginate, alginate-starch, and alginate-starch with chitosan coating as the wall materials. These microcapsules were characterized with regard to the morphology studied by using an optical microscope and scanning electron microscopy (SEM), particle size, and encapsulation efficiency. The microcapsules were then incorporated into the chewing gums. The chewing gums were characterized by thermal behavior (by differential scanning calorimetry [DSC]), texture profile analysis [TPA], and sensory evaluation. Furthermore, the release of caffeine from the chewing gum was studied in vitro using the masticatory simulator and in vivo by a chew-out study. The microcapsules revealed a spherical form and high encapsulation efficiency, representing the success of the technique. The outcomes indicated that it is possible to encapsulate caffeine with the techniques employed and the microcapsules prolonged the release of caffeine throughout mastication. The chewing gum containing alginate-starch with chitosan-coated microcapsules showed the great potential of the microcapsule in controlling the release of the caffeine from the chewing gum, thereby delaying its bitterness. 相似文献
13.
The purpose of this research was to mask the bitter taste of Diphenhydramine Hydrochloride (DPH) using cation exchange resins.
Indion 234 and Tulsion 343 that contained crosslinked polyacrylic backbone were used. The drug resin complexes (DRC) were
prepared by batch process by taking drug: resin ratios 1:1, 1:2, and 1:3. The optimum drug: resin ratio and the time required
for maximum complexation was determined. The drug resinates were evaluated for the drug content, taste, micromeritic properties
drug release and X-ray diffraction (PXRD). Effervescent and dispersible tablets were developed from optimum drug: resin ratios
of 1:2 and 1:1. The formulations were evaluated for uniformity of dispersion, disintegration time, and in vitro dissolution. The X-ray diffraction study confirmed the monomolecularity of entrapped drug in the resin beads. The taste evaluation
depicted the successful taste masking of DPH with drug resin complexes. The drug release of 95% in 15 min was observed for
effervescent and dispersible tablets. 相似文献
14.
Formulation Development and Bioavailability Evaluation of a Self-Nanoemulsified Drug Delivery System of Oleanolic Acid 总被引:1,自引:0,他引:1
Jia Xi Qi Chang Chak K. Chan Zhao Yu Meng Geng Nan Wang Jia Bei Sun Yi Tao Wang Henry H. Y. Tong Ying Zheng 《AAPS PharmSciTech》2009,10(1):172-182
This study aims to formulate and evaluate bioavailability of a self-nanoemulsified drug delivery system (SNEDDS) of a poorly
water-soluble herbal active component oleanolic acid (OA) for oral delivery. Solubility of OA under different systems was
determined for excipient selection purpose. Four formulations, where OA was fixed at the concentration of 20 mg/g, were prepared
utilizing Sefsol 218 as oil phase, Cremophor EL and Labrasol as primary surfactants, and Transcutol P as cosurfactant. Pseudo-ternary
phase diagrams were constructed to identify self-emulsification regions for the rational design of SNEDDS formulations. Sefsol
218 was found to provide the highest solubility among all medium-chained oils screened. Efficient self-emulsification was
observed for the systems composing of Cremophor EL and Labrasol. The surfactant to cosurfactant ratio greatly affected the
droplet size of the nanoemulsion. Based on the outcomes in dissolution profiles, stability data, and particle size profiles,
three optimized formulations were selected: Sefsol 218/Cremophor EL/Labrasol (50:25:25, w/w), Sefsol 218/Cremophor EL/Labrasol/Transcutol P (50:20:20:10, w/w), and Sefsol 218/Cremophor EL/Labrasol/Transcutol P (50:17.5:17.5:15, w/w). Based on the conventional dissolution method, a remarkable increase in dissolution was observed for the SNEDDS when compared
with the commercial tablet. The oral absorption of OA from SNEDDS showed a 2.4-fold increase in relative bioavailability compared
with that of the tablet (p < 0.05), and an increased mean retention time of OA in rat plasma was also observed compared with that of the tablet (p < 0.01). These results suggest the potential use of SNEDDS to improve dissolution and oral bioavailability for poorly water-soluble
triterpenoids such as OA. 相似文献
15.
E. V. Syutkina A. V. Masalov A. G. Gamburtsev A. V. Faleev O. V. Oleinik S. I. Aleksandrov 《Human physiology》2002,28(6):715-721
The study of the dynamics of the variables of physical development of neonates in the first months of life and geomagnetic field fluctuations in the period from 1990 to 2001 demonstrated their complex rhythmic structure. In the studied series of birth weight and the parameters of the 84-h rhythms of daily body weight gain, as well as the parameters of the 84-h rhythms of the K-index, there are ranges of increased spectral density coinciding in frequency. In these intervals (1.1–1.3 and 5–10 years), the temporal behavior of the series of physiological and geomagnetic variables is correlated. 相似文献
16.
The aim of this study was to investigate the effects of formulation and process variables on the properties of niosomes formed from Span 40 as nonionic surfactant. A variety of formulations encapsulating Paclitaxel, a hydrophobic model drug, were prepared using different dicetyl phosphate (DCP) and Span 40-cholesterol (1:1) amounts. Formulations were optimized by multiple regression analysis to evaluate the changes on niosome characteristics such as entrapment efficiency, particle size, polydispersity index, zeta potential and in vitro drug release. Multiple regression analysis revealed that as Span 40-cholesterol amounts in the formulations were increased, zeta potential and percent of drug released at 24th hour were decreased. Besides, DCP was found to be effective on increasing niosome size. As a process variable, the effect of sonication was observed and findings revealed an irreversible size reduction on Span 40 niosomes after probe sonication. Monodisperse small sized (133 ± 6.01 nm) Span 40 niosomes entrapping 98.2% of Paclitaxel with a weight percentage of 3.64% were successfully prepared. The drug–excipient interactions in niosomes were observed by differential scanning calorimetry and X-ray powder diffraction analysis. Both techniques suggest the conversion of PCTs’ crystal structure to amorphous form. The thermal analyses demonstrate the high interaction between drug and surfactant that explains high entrapment efficiency. After 3-month storage, niosomes preserved their stability in terms of drug amount and particle size. Overall, this study showed that Span 40 niosomes with desired properties can be prepared by changing the content and production variables.Key words: drug delivery systems, drug release, multiple regression, niosomes, paclitaxel 相似文献
17.
The objective of this study was to develop a solid dispersion based controlled release system for drug substances that are poorly soluble in water. A wax-based disintegration mediated controlled release system was designed based on the fact that an amorphous drug can crystallize out from hydrophilic matrices. For this study, cilostazol (CIL) was selected as the model drug, as it exhibits poor aqueous solubility. An amorphous solid dispersion was prepared to assist the drug to attain a supersaturated state. Povidone was used as carrier for solid dispersion (spray drying technique), hydrogenated vegetable oil (HVO) as wax matrix former, and sodium carboxymethyl cellulose (NaCMC) as a disintegrant. The extreme vertices mixture design (EVMD) was applied to optimize the designed and developed composition. The optimized formulation provided a dissolution pattern which was equivalent to the predicted curve, ascertaining that the optimal formulation could be accomplished with EVMD. The release profile of CIL was described by the Higuchi’s model better than zero-order, first-order, and Hixson-Crowell’s model, which indicated that the supersaturation state of CIL dominated to allow drug release by diffusion rather than disintegration regulated release as is generally observed by Hixson-Crowell’s model. The optimized composition was evaluated for disintegration, dissolution, XRD, and stability studies. It was found that the amorphous state as well as the dissolution profile of CIL was maintained under the accelerated conditions of 40°C/75% RH for 6 months.KEY WORDS: cilostazol, controlled release, disintegration-mediated controlled release (DMCR), extreme vertices mixture design (EVMD), solid dispersion 相似文献
18.
Meiwan Chen Jiannan Lu Weibin Deng Abhilasha Singh Noorullah Naqvi Mohammed Michael A. Repka Chuanbin Wu 《AAPS PharmSciTech》2014,15(3):522-529
This study investigated the processing parameters and formulation factors on the bioadhesive properties, temperature stability properties, and drug release properties of miconazole in PolyOx® and Klucel® matrix systems produced by Hot-melt Extrusion (HME) technology. Miconazole incorporated into these matrix systems were found to be stable for 8 months by X-ray diffraction (XRD). The addition of miconazole increased area under the curve (AUC) at contact time intervals of 30 and 60 sec, while the bioadhesion decreased with an increase in processing temperatures. The release profiles suggest that a sustained release of miconazole was observed from all of the tested HME film formulations for approximately 10 h. The release from the optimal HME film extruded at 205°C was found to be significantly different than that extruded at 190°C. Therefore, this matrix system may address the present shortcomings of currently available therapy for oral and pharyngeal candidiasis. 相似文献
19.
A. Bartkowiak S. sukasik K. Chwistecki 《Biometrical journal. Biometrische Zeitschrift》1991,33(6):711-718
The evaluation is based on the clinic trial with gemfibrosil (“Gevilon”, Parke-Davis) carried out in a group of 48 patients, to whom the drug was administered in the single dose of 900 mg daily during the period of 3 months. In this paper we show the results of the treatment on five biochemical Coronary Heart Disease (CHD) risk variables: Cholesterol (CHOL), High Density Lipoprotein (HDL), Triglyccrides (TGL), Uric Acid (UA) and Glucose (GL). We are concerned with a statistical model allowing to predict which and how large changes in the considered variable can be expected in a patient taking the drug. This is done considering the “regression to the mean” effect. 相似文献
20.
Meka Lingam Thadisetty Ashok Vobalaboina Venkateswarlu Yamsani Madhusudan Rao 《AAPS PharmSciTech》2008,9(4):1253-1261
A biphasic gastroretentive floating drug delivery system with multiple-unit mini-tablets based on gas formation technique
was developed to maintain constant plasma level of a drug concentration within the therapeutic window. The system consists
of loading dose as uncoated core units, and prolonged-release core units are prepared by direct compression process; the latter
were coated with three successive layers, one of which is seal coat, an effervescent (sodium bicarbonate) layer, and an outer
polymeric layer of polymethacrylates. The formulations were evaluated for quality control tests, and all the parameters evaluated
were within the acceptable limits. The system using Eudragit RL30D and combination of them as polymeric layer could float
within acceptable time. The drug release was linear with the square root of time. The rapid floating and the controlled release
properties were achieved in this present study. When compared with the theoretical release profile, the similarity factor
of formulation with coating of RS:RL (1:3)–7.5%, was observed to be 74, which is well fitted into zero-order kinetics confirming
that the release from formulation is close to desired release profile. The stability samples showed no significant change
in dissolution profiles (p > 0.05). In vivo gastric residence time was examined by radiograms, and it was observed that the units remained in the stomach for about 5 h. 相似文献