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1.
Providing pH-independent oral release of weakly basic drugs with conventional matrix tablets can be challenging because of the pH-dependent solubility characteristics of the drugs and the changing pH environment along the gastrointestinal tract. The aim of the present study was to use a hydrophobic polymer to overcome the issue of pH-dependent release of weakly basic model drug verapamil hydrochloride from matrix tablets without the use of organic buffers in the matrix formulations. Silicone pressure-sensitive adhesive (PSA) polymer was evaluated because of its unique properties of low surface energy, hydrophobicity, low glass transition temperature, high electrical resistance, and barrier to hydrogen ion diffusion. Drug release, hydrogen ion diffusion, tablet contact angle, and internal tablet microenvironment pH with matrix tablets prepared using PSA were compared with those using water-insoluble ethyl cellulose (EC). Silicone PSA films showed higher resistance to hydrogen ion diffusion compared with EC films. Verapamil hydrochloride tablets prepared using silicone PSA showed higher hydrophobicity and lower water uptake than EC tablets. Silicone PSA tablets also showed pH-independent release of verapamil and decreased in dimensions during drug dissolution. By contrast, verapamil hydrochloride tablets prepared using EC did not achieve pH-independent release.  相似文献   

2.
A novel drug-in-adhesive matrix was designed and prepared. A thermoplastic elastomer, styrene–isoprene–styrene (SIS) block copolymer, in combination with tackifying resin and plasticizer, was employed to compose the matrix. Capsaicin was selected as the model drug. The drug percutaneous absorption, adhesion properties, and skin irritation were investigated. The results suggested that the diffusion through SIS matrix was the rate-limiting step of capsaicin percutaneous absorption. [SI] content in SIS and SIS proportions put important effects on drug penetration and adhesion properties. The chemical enhancers had strong interactions with the matrix and gave small effect on enhancement of drug skin permeation. The in vivo absorption of samples showed low drug plasma peaks and a steady and constant plasma level for a long period. These results suggested that the possible side effects of drug were attenuated, and the pharmacological effects were enhanced with an extended therapeutic period after application of SIS matrix. The significant differences in pharmacokinetic parameters produced by different formulations demonstrated the influences of SIS copolymer on drug penetrability. Furthermore, the result of skin toxicity test showed that no skin irritation occurred in guinea pig skin after transdermal administration of formulations.Key words: adhesion, in vivo absorption, skin irritation, thermoplastic elastomer, transdermal drug delivery  相似文献   

3.
A newly available polyvinylacetate aqueous dispersion, Kollicoat SR 30D, was evaluated with respect to its ability to modulate the in vitro release of a highly water-soluble model compound (diphenhydramine hydrochloride) from nonpareil-based systems. Kollicoat SR 30D premixed with a selected plasticizer (10% wt/wt propylene glycol, 2.5% triethyl citrate, or 2.5% dibutyl sebacute), talc, and red #30 lake dye was coated onto the drug beads in an Aeromatic Strea I fluid-bed drier with a Wurster insert using bottom spray. With propylene glycol as the plasticizer, increases in polymer coating level retarded drug release from beads in a stepwise fashion along with apparent permeability, indicating a consistent release mechanisms. Stability studies at 40°C/75% RH revealed gradual decreases in dissolution rate, and additional curing studies further confirmed the dependence of release kinetics on curing condition. Furthermore, the type of plasticizer was found to play a key role. Unplasticized formulations exhibited the fastest dissolution, followed by formulations plasticized with triethyl citrate, propylene glycol, and dibutyl sebacate. All 4 formulations (unplasticized and plasticized), nevertheless, revealed a marked difference between uncured and cured dissolution profiles. Kollicoat SR 30D has, thereby, been demonstrated to effectively retard drug release from nonpareilbased systems. However, selected plasticizer type and subsequent curing condition play important roles in controlling drug release from such a system.  相似文献   

4.
This study focused on investigating and comparing between the effect of the strongly cationic exchange resin, Dowex 88 (Dow88), and the weakly cationic exchange resin, Amberlite IRP64 (Am64), on the physical properties of matrices and their drug release profiles. The matrices were prepared by direct compression of Methocel K4M (HPMC) or Ethocel 7FP (EC) polymeric matrix formers and contained diphenhydramine hydrochloride as a model drug. The addition of Dow88 to the matrices decreased matrix hardness and increased thickness, diameter, and friability. In contrast, the addition of Am64 increased matrix hardness and maintained the original thickness, diameter, and friability. In deionized water, both resins lowered drug release from HPMC-based matrices by virtue of the gelation property of matrix former and the drug exchange property of embedded resin, in other words in situ resinate formation. Dow88 strongly dissociated and lowered the drug release to a greater extent than Am64, which was weakly dissociated. However, Am64 could retard drug release under simulated gastrointestinal conditions. EC-based matrices containing either resin displayed a propensity for disintegration caused by swelling and wicking (water adsorption) actions by the resin. The results of this study provided useful information on the utilization of ion exchange resins as release modifiers in matrix systems.  相似文献   

5.
The present study was performed to design oral controlled delivery systems for the water-soluble drug, verapamil hydrochloride, using natural and semisynthetic polymers as carriers in the forms of 1- and 3-layer matrix tablets. Verapamil hydrochloride 1-layer matrix tablets containing hydroxypropylmethylcellulose, tragacanth, and acacia either alone or mixed were prepared by direct compression technique. 3-layer matrix tablets were prepared by compressing the polymers as release retardant layers on both sides of the core containing the drug. The prepared tablets were subjected to in vitro drug release studies. Tragacanth when used as the carrier in the formulation of 1- and 3-layer matrices produced satisfactory release prolongation either alone or in combination with the other 2 polymers. On the other hand, acacia did not show enough prolonging efficiency in 1- and 3-layer matrix tablets. The results also showed that the location of the polymers in the 3-layer tablets has a pronounced effect on the drug release. Kinetic analysis of drug release from matrices exhibiting sustained release indicated that release was predominantly attributable to the contribution made by Fickian diffusion, while the erosion/relaxation mechanisms had a minor role in the release. Published: December 7, 2005  相似文献   

6.
Psyllium, a medicinally active natural polysaccharide, has been modified with polyacrylamide to develop the hydrogels; those can act as the potential candidate for novel drug delivery systems. In the present studies, the release dynamics of model drugs (salicylic acid and tetracycline hydrochloride) from the drug-loaded hydrogels have been discussed, for the evaluation of the drug release mechanism and diffusion coefficients. It has been observed that diffusion exponent ‘n’ have 0.68 and 0.74 values and gel characteristic constant ‘k’ have 1.625 × 10−2 and 1.272 × 10−2 values, respectively, for the release of salicylic acid and tetracycline hydrochloride in distilled water from the drug loaded hydrogels. Therefore, drug release from the drug loaded hydrogels through Non-Fickian or Anomalous diffusion mechanism where the rate of drug diffusion and rate of polymer relaxation were comparable. The effect of pH on the release pattern of tetracycline has been studied by varying the pH of the release medium. However, in each release medium, the Initial diffusion coefficient was observed to be more than the late time diffusion coefficient.  相似文献   

7.
Three drugs, a non-steroid anti-inflammatory drug sodium salicylate, an analgesic propoxyphene hydrochloride and an antipyretic-analgesic acetaminophen were administered orally to patients undergoing mid-trimester hypertonic saline induced abortion to determine analgesic potency and the effect on the instillation/abortion time interval (I/ATI). Sodium salicylate (structurally related to acetylsalicylic acid, aspirin) and propoxyphene hydrochloride did not prolong the I/ATI. Acetaminophen, reportedly free of anti-inflammatory activity, prolonged the I/ATI. Clinically, acetaminophen and propoxyphene appeared to provide better analgesia than sodium salicylate. The hypothesized relationship of the three drugs to suppression of prostaglandin biosynthesis is presented.  相似文献   

8.
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   

9.
Anionic polymer sodium carboxymethylcellulose (CELLOGEN® HP-HS and/or HP-12HS) was investigated for its ability to influence the release of three model drugs propranolol hydrochloride, theophylline and ibuprofen from polyethylene oxide (POLYOX™ WSR 1105 and/or Coagulant) hydrophilic matrices. For anionic ibuprofen and non-ionic theophylline, no unusual/unexpected release profiles were obtained from tablets containing a mixture of two polymers. However, for cationic propranolol HCl, a combination of polyethylene oxide (PEO) with sodium carboxymethylcellulose (NaCMC) produced a significantly slower drug release compared to the matrices with single polymers. The potential use of this synergistic interaction can be a design of new extended release pharmaceutical dosage forms with a more prolonged release (beyond 12 h) using lower polymer amount, which could be particularly beneficial for freely water-soluble drugs, preferably for once daily oral administration. In order to explain changes in the obtained drug release profiles, Fourier transform infrared absorption spectroscopy was performed. A possible explanation for the more prolonged propranolol HCl release from matrices based on both PEO and NaCMC may be due to a chemical bond (i.e. ionic/electrostatic intermolecular interaction) between amine group of the cationic drug and carboxyl group of the anionic polymer, leading to a formation of a new type/form of the active (i.e. salt) with sustained release pattern.Key words: extended release, FT-IR, ibuprofen, matrix tablet, polyethylene oxide, polymer combination, propranolol hydrochloride, sodium carboxymethylcellulose, theophylline  相似文献   

10.
The objective of this study was to investigate the release behaviour of propranolol hydrochloride from psyllium matrices in the presence hydrophilic polymers. The dissolution test was carried out at pH 1.2 and pH 6.8. Binary mixtures of psyllium and hydroxypropyl methylcellulose (HPMC) used showed that an increase in the percentage of HPMC in the binary mixtures caused a significant decrease in the release rate of propranolol. Psyllium–alginate matrices produced lower drug release as compared to when the alginate was the matrix former alone. When sodium carboxy methyl cellulose (NaCMC) was incorporated into the psyllium, the results showed that matrices containing the ratio of psyllium–NaCMC in the 1:1 ratio are able to slow down the drug release significantly as compared to matrices made from only psyllium or NaCMC as retardant agent suggesting that there could be a synergistic effect between psyllium and NaCMC. The double-layered tablets showed that the psyllium and HPMC in the outer shell of an inner formulation of psyllium alone had the greatest effect of protecting the inner core and thus producing the lowest drug release (DE = 38%, MDT = 93 min). A significant decrease in the value of n in Q = kt n from 0.70 to 0.51 as the psyllium content was increased from 50 to 150 mg suggests that the presence of psyllium in HPMC matrices affected the release mechanism. Psyllium powder had the ability in the combination with other hydrophilic polymers to produce controlled release profiles. Care and consideration should as such be taken when formulating hydrophilic matrices in different combinations.  相似文献   

11.
We studied the release of salbutamol and ketoprofen enantiomers from HPMC K100M matrices containing two types of cellulose derivatives: cellulose tris (3,5-dimethylphenylcarbamate) and cellulose tris (2,3-dichlorophenylcarbamate), chiral excipients used as stationary phases for liquid chromatography. These matrices provided an extended release of both drugs. Ketoprofen release from formulations elaborated with cellulose tris (2,3-dichlorophenylcarbamate) was by anomalous transport, because the value of n (release exponent of the diffusion equation) ranged between 0.60-0.68, whereas for all other formulations the value of exponent n ranged from 0.50-0.54. The drug thus diffuses through the matrix and is released following a quasi-Fickian diffusion mechanism (stereoselective process). The matrices preferentially retained R-salbutamol and S-ketoprofen and cellulose tris (3,5-dimethylphenylcarbamate) showed more capacity of chiral discrimination for both drugs than cellulose tris (2,3-dichlorophenylcarbamate). Moreover, we observed that stereoselectivity is dependent on the amount of chiral excipient in the formulation. Diffusion tests confirmed the chiral interaction between drugs and cellulose derivatives observed in the dissolution assays except for matrices elaborated with ketoprofen and cellulose tris (2,3-dichlorophenylcarbamate), where the low stereoselectivity observed with the matrices is due to the presence of HPMC K100M. We conclude that the inclusion of these cellulose derivatives in HPMC matrices does not result in a relevant stereoselectivity with respect to the two drugs studied.  相似文献   

12.
Sustained-release matrix tablets based on Eudragit RL and RS were manufactured by injection moulding. The influence of process temperature; matrix composition; drug load, plasticizer level; and salt form of metoprolol: tartrate (MPT), fumarate (MPF) and succinate (MPS) on ease of processing and drug release were evaluated. Formulations composed of 70/30% Eudragit RL/MPT showed the fastest drug release, substituting part of Eudragit RL by RS resulted in slower drug release, all following first-order release kinetics. Drug load only affected drug release of matrices composed of Eudragit RS: a higher MPT concentration yielded faster release rates. Adding triethyl citrate enhanced the processability, but was detrimental to long-term stability. The process temperature and plasticizer level had no effect on drug release, whereas metoprolol salt form significantly influenced release properties. The moulded tablets had a low porosity and a smooth surface morphology. A plasticizing effect of MPT, MPS and MPF on Eudragit RS and Eudragit RL was observed via DSC and DMA. Solubility parameter assessment, thermal analysis and X-ray diffraction demonstrated the formation of a solid solution immediately after production, in which H-bonds were formed between metoprolol and Eudragit as evidenced by near-infrared spectroscopy. However, high drug loadings of MPS and MPF showed a tendency to recrystallise during storage. The in vivo performance of injection-moulded tablets was strongly dependent upon drug loading.  相似文献   

13.
In situ gelling systems are very attractive for pharmaceutical applications due to their biodegradability and simple manufacturing processes. The synthesis and characterization of thermosensitive poly(D,L-lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-PLGA triblock copolymers as in situ gelling matrices were investigated in this study as a drug delivery system. Ring-opening polymerization using microwave irradiation was utilized as a novel technique, and the results were compared with those using a conventional method of polymerization. The phase transition temperature and the critical micelle concentration (CMC) of the copolymer solutions were determined by differential scanning calorimetry and spectrophotometry, respectively. The size of the micelles was determined with a light scattering method. In vitro drug release studies were carried out using naltrexone hydrochloride and vitamin B12 as model drugs. The rate and yield of the copolymerization process via microwave irradiation were higher than those of the conventional method. The copolymer structure and concentration played critical roles in controlling the sol-gel transition temperature, the CMC, and the size of the nanomicelles in the copolymer solutions. The rate of drug release could be modulated by the molecular weight of the drugs, the concentration of the copolymers, and their structures in the formulations. The amount of release versus time followed zero-order release kinetics for vitamin B12 over 25 days, in contrast to the Higuchi modeling for naltrexone hydrochloride over a period of 17 days. In conclusion, PLGA-PEG1500-PLGA with a lactide-to-glycolide ratio of 5:1 is an ideal system for the long-acting, controlled release of naltrexone hydrochloride and vitamin B12.  相似文献   

14.
In this study, ethylcellulose (EC)-based microsphere formulations were prepared without and with triethyl citrate (TEC) content of 10% and 30% by water-in-oil emulsion-solvent evaporation technique. Diltiazem hydrochloride (DH) was chosen as a hydrophilic model drug and used at different drug/polymer ratios in the microspheres. The aim of the work was to evaluate the influence of plasticizer ratio on the drug release rate and physicochemical characteristics of EC-based matrix-type microspheres. The resulting microspheres were evaluated for encapsulation efficiency, particle size and size distribution, surface morphology, total pore volume, thermal characteristics, drug release rates, and release mechanism. Results indicated that the physicochemical properties of microspheres were strongly affected by the drug/polymer ratio investigated and the concentration of TEC used in the production technique. The surface morphology and pore volume of microspheres significantly varied based on the plasticizer content in the formulation. DH release rate from EC-based matrix-type microspheres can be controlled by varying the DH to polymer and plasticizer ratios. Glass transition temperature values tended to decrease in conjunction with increasing amounts of TEC. Consequently, the various characteristics of the EC microspheres could be modified based on the plasticized ratio of TEC.  相似文献   

15.
目的:研究盐酸小檗碱缓释片的配方与制备方法,考察其释放度。方法:以盐酸小檗碱释放度为考察指标,采用单因素试验法,考察了羟丙基甲基纤维素(HPMC)和乳糖的用量对药物体外释放行为的影响,并采用正交设计实验对处方进行优化,确定最佳处方。结果:最佳配方为HPMC-K4M的用量为10%,乳糖用量为20%,PVP的用量为3%,微晶纤维素的用量为20%。2 h累积释药量为30%,6 h累积释药量为60%,12 h累积释药量为90%。结论:按最佳配方制备的盐酸小檗碱缓释片有较好的缓释行为,基本上能满足缓释片的释放要求。  相似文献   

16.
Preparation of an intelligent drug delivery system which releases the drug in response to the environmental stimuli in a controlled manner is one of the interesting subjects and it is the purpose of this study. Films composed of Eudragit RS and different percentages of plasticizers (0%, 5%, 10%, or 20% w/w based on polymer weight), poly ethylene glycol 400 or triethyl citrate (TEC), were prepared by solvent casting method. Glass transition temperatures of the films were determined by differential scanning colorimetery. Water uptake and drug permeation through membranes with the glass transition temperature (Tg) close to the body temperature were investigated. Propranolol hydrochloride and acetaminophen were used as model drugs in permeation studies. The results showed that Eudragit RS films with 20% of either plasticizer showed thermo-responsivity around body temperature. The water uptake of the films and the permeation rates of both drugs increased at temperatures above the Tg of the films. The films containing TEC was found to be more appropriate thermo-responsive membrane due to a higher sensitivity to temperature and more ability to control drug release.  相似文献   

17.
β-cyclodextrins (βCD) are cyclic oligosaccharides which have been widely employed for pharmaceutical applications. Discs of insoluble polymers were synthesized by crosslinking β-cyclodextrins with the reagent epichlorohydrin. In this work, the possibility of employing a polymer containing 60 ± 3% βCD for drug delivery of two antiinflammatory (naproxen and nabumetone) and two antifungal drugs (naftifine and terbinafine) has been investigated. The interaction of Naproxen with the polymers was evidenced by X-ray diffractometry, FTIR spectroscopy and differential thermal analysis. Drug release kinetics were carried out at physiological conditions of pH and temperature, and kinetic and diffusion constants were calculated by fitting 60% of the release profile according to the Korsmeyer-Peppas equation. Also, diffusion coefficients were calculated according to the simplified Higuchi model. The drug release followed a simple Fickian diffusion mechanism for all the model drugs. This study suggests that these hydrogel matrices are potentially suitable as sustained release systems.  相似文献   

18.
This study aimed to investigate the effects of dry and humid heat curing on the physical and drug release properties of polyvinyl acetate–polyvinyl pyrrolidone matrices. Both conditions resulted in increased tablet hardness; tablets stored under humid conditions showed high plasticity and deformed during hardness testing. Release from the matrices was dependent on the filler's type and level. Release profiles showed significant changes, as a result of exposure to thermal stress, none of the fillers used stabilized matrices against these changes. Density of neat polymeric compacts increased upon exposure to heat; the effect of humid heat was more evident than dry heat. Thermograms of samples cured under dry heat did not show changes, while those of samples stored under high humidity showed significant enlargement of the dehydration endotherm masking the glass transition of polyvinyl acetate. The change of the physical and release properties of matrices could be explained by the hygroscopic nature of polyvinyl pyrrolidone causing water uptake; absorbed water then acts as a plasticizer of polyvinyl acetate promoting plastic flow, deformation, and coalescence of particles, and altering the matrices internal structure. Results suggest that humid heat is more effective as a curing environment than dry heat for polyvinyl acetate–polyvinyl pyrrolidone matrices.  相似文献   

19.
In order to utilize the psyllium husk a medicinally important natural polysaccharide and to develop the novel hydrogels meant for the colon specific drug delivery, we have prepared psyllium and methacrylamide based polymeric networks by using N,N′-methylenebisacrylamide (NN-MBAAm) as crosslinker and ammonium persulfate (APS) as initiator. To study various structural aspects of the polymeric networks thus formed psy-cl-poly(MAAm), these were characterized with SEMs, FTIR, TGA and swelling studies. The swelling studies of networks were carried out as a function of time, temperature, pH and [NaCl]. Equilibrium swelling has been observed to depend on both composition of the polymer and nature of swelling medium. Maximum percent swelling 1262 was observed for the polymeric network prepared with 19.45 × 10−3 mol/L of [NN-MBAAm] at 40 °C in 0.5 M NaOH solution. This article also discusses the release dynamics of tetracycline hydrochloride from the hydrogels, for the evaluation of the drug release mechanism and diffusion coefficients of drug from the polymer matrix. The effect of pH on the release pattern of tetracycline hydrochloride has been studied by varying the pH of the release medium. It has been observed from the release dynamics of drug from the hydrogels that the diffusion exponent ‘n’ have 0.477, 0.423 and 0.427 values and gel characteristic constant ‘k’ have 5.07 × 10−2, 6.34 × 10−2 and 6.38 × 10−2 values, respectively, in distilled water, pH 2.2 buffer and pH 7.4 buffer solution. The values the ‘n’ indicated that the Fickian type diffusion mechanism occurred for the release of tetracycline hydrochloride from drug loaded psy-cl-poly(MAAm) polymers in different release mediums. In Fickian type diffusion mechanism, the rate of polymer chain relaxation is more as compare to the rate of drug diffusion from these hydrogels and release behavior follows Fick’s law of diffusion. In each release medium, the values of the initial diffusion coefficient ‘Di’ for the release of tetracycline hydrochloride was higher than the values of late time diffusion coefficient ‘DL’ indicating that in the start, the diffusion of drug from the polymeric matrix was faster as compare to the latter stages.  相似文献   

20.
Colon targeting drug delivery systems have attracted many researchers due to the distinct advantages they present such as near neutral pH, longer transit time and reduced enzymatic activity. Moreover, in recent studies, colon specific drug delivery systems are gaining importance for use in the treatment of local pathologies of the colon and also for the systemic delivery of protein and peptide drugs.In previous works, our group has developed different types of hydrophilic matrices with grafted copolymers of starch and acrylic monomers with a wide range of physicochemical properties which have demonstrated their ability in controlled drug release. Since the cost of synthesizing a new polymeric substance and testing for its safety is enormous, polymer physical blends are frequently used as excipients in controlled drug delivery systems due to their versatility. So, the aim of this work is to combine two polymers which offer different properties such as permeability for water and drugs, pH sensitivity and biodegradability in order to further enhance the release performance of various drugs. It was observed that these physical blend matrices offer good controlled release of drugs, as well as of proteins and present suitable properties for use as hydrophilic matrices for colon-specific drug delivery.  相似文献   

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