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1.
ABSTRACT

The release profiles of flurbiprofen (F) from different gel and ointment formulations were studied in order to evaluate factors governing the release process. Carbopol 934P (CAB), poloxamer 407 (POL), and eudragit S100 (EUD) gel bases were used, while emulsion (EML) and polyethylene glycol (PEG) ointments were employed. The release studies were conducted using membraneless diffusion cells and lipophilic receptor medium, isopropyl myristate (IPM). The effects of gelling agent concentrations and the initial drug load on drug release were determined. Hydrogels were observed to give higher amounts of drug release than hydrophobic EUD gel and ointments, despite the lower bulk viscosity of these bases. Flurbiprofen release from CAB gels was 3.06–1.56-fold higher than from other formulations. Over a 4-hr period, the amount of F released was 492.8 and 316.0 µg/cm2 from 2% CAB and 25% POL gels, while it was 213.05, 168.61, and 160.9 µg/cm2 from EML, 40% EUD, and PEG bases, respectively. The diffusivity of F in the gel bases was an inverse function of the polymer concentrations over the range of 1–3% CAB, 20–30% POL, and 35–45% EUD gels. Drug release was increased from the bases as the initial F concentration increased over the range 0.25–1.0%, while the diffusion coefficient observed an inverse relationship. The CAB and POL gels could be the vehicles of choice for the rapid release and onset of F after topical application.  相似文献   

2.
Seven semisolid fill bases were selected for the formulation of 24 capsule formulations, each containing 100 mg of phenytoin sodium. The fill materials were selected based on the water absorption capacity of their mixtures with phenytoin sodium. The fill matrices included lipophilic bases (castor oil, soya oil, and Gelucire (G) 33/01), amphiphilic bases (G 44/14 and Suppocire BP), and water-soluble bases (PEG 4000 and PEG 6000). The drug:base ratio was 1:2. Excipients such as lecithin, docusate sodium, and poloxamer 188 were added to some formulations. The dissolution rate study indicated that formulations containing lipophilic and amphiphilic bases showed the best release profiles. These are F4 (castor oil-1% docusate sodium); F10 (castor oil-3% poloxamer 188); F14 (G33/01-10% lecithin); F17 (G33/01-1% docusate sodium), and F20 (Suppocire BP). Further, the dissolution stability of the five formulations above was assessed by an accelerated stability study at 30°C and 75% RH using standard Epanutin capsules for comparison. The study included the test and standard capsules either packed in the container of marketed Epanutin capsules (packed) or removed from their outer pack (unpacked). Release data indicated superior release rates of castor oil based formulations (F4 and F10) relative to standard capsules in both the unpacked and packed forms. For instance, the extent of drug release at 30 min after 1 month was 91% for F4 and F10 and 20% for standard capsules. Drug release from packed capsules after 6 months storage was 88% for both formulations F4 and F10 and 35% for standard capsules. In conclusion, the pharmaceutical quality of phenytoin sodium capsules can be improved by using a semisolid lipophilic matrix filled in hard gelatin capsules.  相似文献   

3.
The purpose of this study was to investigate the effect of carvone on the permeation of nicardipine hydrochloride across the excised rat abdominal epidermis from 2% w/w hydroxypropyl cellulose (HPC) gel system. The HPC gel formulations containing nicardipine hydrochloride (1% w/w) and selected concentrations of carvone (0 to 12% w/w) were prepared, and evaluated for drug content, stability of the drug, and in vitro permeation of the drug through excised rat abdominal epidermis. The HPC gel was found to contain 99.98 to 101.6% of nicardipine hydrochloride, and the drug was found to be stable in the HPC gels. The permeation flux of nicardipine hydrochloride across rat epidermis was increased markedly by the addition of carvone to the HPC gels. A maximum flux of nicardipine hydrochloride (243.95.70 ± 1.90 µg/cm2/hr) was observed with an enhancement ratio of 7.9 when carvone was incorporated at a concentration of 12% w/w in the HPC reservoir system. The differential scanning calorimetry and Fourier transform-infrared data indicated that carvone increased the permeability of nicardipine hydrochloride across the rat epidermis by partial extraction of lipids in the stratum corneum. The results suggest that carvone may be useful for enhancing the skin permeability of nicardipine hydrochloride from transdermal therapeutic system containing HPC gel as a reservoir.  相似文献   

4.
Caffeine has recently been found to cure atopic dermatitis, presumably by increasing skin levels of cAMP.In the light of these findings, its release from different ointment bases at varying concentrations was investigated in vitro. The ointment bases used were a petrolatum (named as petrolatum A), a PEG ointment (USP XVIII), a hydrophilic ointment (USP XVIII), and a w/o type emulsifying ointment. It was incorporated into ointment bases at 1,5,10,20 and 30% (w/w) concentrations, by simple trituration technique.

Release experiments were carried out at 37°C, with diffusion cells which were placed in distilled water filled beakers.

For all caffeine concentrations used, the release was highest from the PEG ointment. It decreased with the hydrophilic ointment, the emulsifying ointment, and petrolatum A, in that order. From both petrolatum base and the PEG ointment, release of caffeine increased significantly with increasing concentrations. As for the hydrophilic and emulsifying ointments, release patterns were found to be independent of concentration for some percentages of caffeine.  相似文献   

5.
The study evaluated different mucoadhesive polymeric hydrogels for nasal delivery of acyclovir. Gels containing poly-N-vinyl-2-pyrrolidone (PVP) were prepared with crosslinking achieved by irradiation with a radiation dose of 15 kGy being as efficient as 20 kGy. Gels containing chitosan and carbopol were also evaluated. The mucoadhesive properties of gels were measured by a modification of a classical tensile experiment, employing a tensile tester and using freshly excised sheep nasal mucosa. Considering the mucoadhesive force, chitosan gel and gel prepared with 3% PVP in presence of polyethylene glycol (PEG) 600 were the most efficient. The in vitro drug release depended on the gel composition. Higher release rates were obtained from PVP gels compared to chitosan or carbopol gels. The release rate of drug from PVP gels was increased further in presence of PEG or glycerol. Histopathological investigations proved that the PVP was a safe hydrogel to be used for mucosal delivery. The PEG in gel formulations caused less damages to the nasal mucosal compared to formulation containing glycerol.  相似文献   

6.
The study evaluated different mucoadhesive polymeric hydrogels for nasal delivery of acyclovir. Gels containing poly-N-vinyl-2-pyrrolidone (PVP) were prepared with crosslinking achieved by irradiation with a radiation dose of 15 kGy being as efficient as 20 kGy. Gels containing chitosan and carbopol were also evaluated. The mucoadhesive properties of gels were measured by a modification of a classical tensile experiment, employing a tensile tester and using freshly excised sheep nasal mucosa. Considering the mucoadhesive force, chitosan gel and gel prepared with 3% PVP in presence of polyethylene glycol (PEG) 600 were the most efficient. The in vitro drug release depended on the gel composition. Higher release rates were obtained from PVP gels compared to chitosan or carbopol gels. The release rate of drug from PVP gels was increased further in presence of PEG or glycerol. Histopathological investigations proved that the PVP was a safe hydrogel to be used for mucosal delivery. The PEG in gel formulations caused less damages to the nasal mucosal compared to formulation containing glycerol.  相似文献   

7.
The objective of the present research investigation was to fabricate an acrylate-based transdermal therapeutic system (TTS) of nitrendipine, which could deliver drug at maximum input rate so as to deliver drug in minimum patch size. Transdermal patches were fabricated using synthesized acrylate pressure-sensitive adhesives (PSAs): PSA1, PSA2, and commercially available PSA3 and PSA4 using d-limonene as permeation enhancer. Effect of concentration of d-limonene on permeation kinetics of nitrendipine in PSAs was studied. Fabricated TTS in mentioned PSAs were evaluated for in-vitro release and permeation kinetics through guinea-pig skin. Cumulative release of drug in PSA1, PSA2, PSA3, and PSA4 was observed to be 45%, 40%, 25%, and 25%, respectively, upto 24 hr. Flux of drug through guinea-pig skin calculated at 48 hr in PSA1, PSA2, PSA3, and PSA4, with and without d-limonene, was observed to be 0.346 ± 0.10, 0.435 ± 0.17, 0.410 ± 0.17, and 0.162 ± 0.06, and 0.625 ± 0.19, 1.161 ± 0.46, 0.506 ± 0.17, and 0.520 ± 0.18 (µg/cm2/hr), respectively. The TTS in PSA2 showed comparatively high flux and could deliver drug at high input rate through transdermal route. PSA2 was found to have good rate-controlling property and could be successfully employed in transdermal delivery of nitrendipine.  相似文献   

8.
The percutaneous delivery of nonsteroidal anti-inflammatory drug (NSAID) has the advantages of avoiding the hepatic first pass effect and delivering the drug to the inflammation site at a sustained, concentrated level over an extended period of time. Hydroxypropyl methylcellulose (HPMC) and poloxamer 407 were used in an attempt to develop new topical formulations of pranoprofen. The effects of the drug concentration (0.04, 0.08, 0.12, 0.16, and 0.20%) on the rate of drug release from HPMC-poloxamer 407 gels were examined using a synthetic cellulose membrane at 37±0.5°C. The rate of drug permeation increased significantly with increasing drug concentration in the gels until the concentration reached 0.16%, and increased slightly thereafter. The effects of temperature on the rate of drug release from the 0.16% pranoprofen gels were evaluated at 32, 37, and 42°C. The rate of drug release from the 0.16% pranoprofen gels increased with increasing temperature with activation energy (Ea) of 8.88 kcal/mol. Various penetration enhancers, such as nonionic surfactants and fatty acids, were incorporated in the gel formulation in an attempt to increase the level of drug permeation. Among the enhancers used, octanoic acid had the strongest enhancing effects with an enhancement factor of 3.09. The anti-inflammatory effect of the pranoprofen gel was evaluated using a rat paw-edema model. The 0.16% pranoprofen gel containing octanoic acid as an enhancer reduced the edema size by approximately 73% compared with that of the control group. These results highlight the feasibility of a topical gel formulation of pranoprofen containing an enhancer.  相似文献   

9.
A time-delayed oral drug delivery device was investigated in which an erodible tablet (ET), sealing the mouth of an insoluble capsule, controlled the lag-time prior to drug release. The time-delayed capsule (TDC) lag-time may be altered by manipulation of the excipients used in the preparation of the ET. Erosion rates and drug release profiles from TDCs were investigated with four different excipient admixtures with lactose: calcium sulphate dihydrate (CSD), dicalcium phosphate (DCP), hydroxypropylmethyl cellulose (HPMC; Methocel® K100LV grade) and silicified microcrystalline cellulose (SMCC; Prosolv® 90 grade). Additionally, the compressibility of different insoluble coated capsules was tested at different moisture levels to determine their overall integrity and suitability for oral delivery. Erosion rates of CSD, DCP, and SMCC displayed a nonlinear relationship to their concentration, while HPMC indicated rapid first-order erosion followed by zero-order erosion, the onset of which was dependent on the HPMC concentration. Capsule integrity was confirmed to be most suitable for oral delivery when the insoluble ethyl cellulose coat was applied to a hard gelatin capsule using an organic spray coating process. T50% drug release times varied between 245 (± 33.4) and 393 (± 40.8) minutes for 8% and 20% DCP, respectively, T50% release times of 91 (± 22.1) and 167 (± 34.6) were observed for 8% and 20% CSD; both formulations showed incidence of premature drug release. The SMCC formulations showed high variability due to lamination effects. The HPMC formulations had T50% release times of 69 (± 13.9), 213 (± 25.4), and 325 (± 30.3) minutes for 15%, 24%, and 30% HPMC concentrations respectively, with no premature drug release. In conclusion, HPMC showed the highest reproducibility for a range of time-delayed drug release from the assembled capsule formulation. The method of capsule coating was confirmed to be important by investigation of the overall capsule integrity at elevated humidity levels. The erosion characteristics of ETs containing HPMC may be described by gravimetric loss. The novel time-delayed capsule device presented in this study may be assembled to include an erodible tablet with a known concentration of HPMC. A variety of suitable drugs for targeted chronopharmaceutical therapy can beincorporated into such a device, ultimately improving drug efficacy and patient compliance, and reducing harmful side effects.  相似文献   

10.
An application of carboxymethyl mungbean starch (CMMS) as a gelling agent in the topical pharmaceutical preparation was investigated. CMMS was prepared using specific conditions that yielded a high-viscosity product. Polymer gels and gel bases were prepared at 1-10% (wt/wt), and physicochemical studies were carried out in comparison with four standard gelling agents: carbopol 940 (CP), hydroxypropylmethyl cellulose (HPMC), methyl cellulose (MC), and sodium carboxymethyl cellulose (SCMC). Piroxicam was used as a model drug to study the drug release profile of the gel formulations. The tackless, greaseless, and transparent CMMS gels exhibited pseudoplastic behavior with thixotropy at concentrations less than 5% (wt/wt). At a concentration of 5% (wt/wt) and higher, the semisolid gels showed plastic flow characteristics. Viscosity and X-ray diffraction results indicated a good compatibility between CMMS and the acidic piroxicam. No precipitation of piroxicam or phase separation was observed during a stability test. The release rate of piroxicam from 3% (wt/wt) CMMS gel was 1,003.79 +/- 105.08 microg/cm(2), which was comparable with 947.66 +/- 133.70 microg/cm(2) obtained from a 0.5% (wt/wt) carbopol formulation. The release profiles of both formulations were consistent and remained unchanged after 2 months' storage. Viscosity played an important role in controlling the release rate of low concentration CMMS formulations by regulating the drug diffusion. At a concentration of 5% (wt/wt) CMMS and higher, the release rates of piroxicam were not significantly different. A plausible explanation based on the nature of the gelling agent was proposed. Stability and drug release profiles of CMMS and commercial gelling agents were compared. The results supported the potential use of CMMS as a new, effective gelling agent for topical gel preparation.  相似文献   

11.
Content analysis and stability studies were performed for the commercial products of St. John's wort. Six marketed formulations were analyzed for their hypericin and pseudohypericin content. These products were standardized to contain 0.3% hypericin. Results revealed total hypericin as 7.72-38.57% of the labeled claim with varying concentrations of pseudohypericin. Stability studies were carried out under three different storage conditions: 1) 25 ± 2°C, 60 ± 5%RH for six months, 2) 40 ± 2°C, 75 ± 5%RH for six months, and 3) 50°C for one month. Tablet formulations were also analyzed for their hardness and friability. Stability studies revealed significant decrease in the content of the marker compounds with time.  相似文献   

12.
Porous titanium dioxide (Titania) thin films were grown by anodic oxidation using high purity (99.7%) titanium foil in a dilute sulphuric acid (1 M) medium. The anodization process was carried out for 30 minutes with 20 mA/cm2 and 50 mA/cm2 current densities. The samples were characterized by XRD, SEM, and AFM techniques. It was found that the grown porous titania films were less sensitive to 500 ppm hydrogen in air ambient below 300°C; however, the sensitivity and response behavior of the film at 300°C are very much dependent on the growth conditions. Particularly, the films grown at current density 50 mA/cm2 and 1 M acid concentration exhibited the lowest response time of 151 sec at 300°C.  相似文献   

13.
The objective of this study was to assess average bioequivalence of two immediate released tablet formulations of 500-mg clarithromycin tablets in 24 healthy Thai male volunteers. In a randomized, single dose, fasting state, two-period, crossover study design with a 1-week washout period, each subject received a 500-mg clarithromycin tablet. Plasma samples were collected over a 24-hour period after oral administration and were analyzed by using a validated method using high performance liquid chromatography with electrochemical detection. Pharmacokinetic parameters were determined by using noncompartmental analysis. The time to reach the maximal concentration (tmax, h), the peak concentration (Cmax, ng/mL), and the area under the curve (AUC0 - ∞, ng.h/mL) of the Reference and Test formulations were 2.0 ± 0.8 vs. 2.2 ± 0.9, 2793 ± 1338 vs. 2642 ± 1344, and 17912 ± 7360 vs. 17660 ± 7992, respectively. Relative bioavailability was 0.99. The 90% confidence interval of Cmax and AUC0 - ∞ were 82.6-112.1% and 84.7-112.0%. Bioequivalence between the Test and Reference formulation can be concluded.  相似文献   

14.
The in- vitro release of Naproxen from various ointment bases, including a water-washable base with the drug in the water phase (I) and the drug in the oil phase (II), a hydrophilic base with the drug in the water phase (III), and the drug in the oil phase (IV), and an anhydrous ointment (V), a gel (VI) and a modified University of California (U .C .H.) base (VII) were studied. In addition, the effects of various additives (urea, ethanol, dimethyl sulfoxide and polyethylene glycol-400) on the release of Naproxen from formulations (I) and (II) were determined. Low concentrations of urea and ethanol in the formulations increased the release of the drug from both these bases, however, higher concentrations adversely affected the release of the drug. While dimethyl sulfoxide (DMSO) had no significant effect on the drug release, the inclusion of polyethylene glycol-400 in both bases decreased the release of Naproxen.

The percutaneous absorption of Naproxen from the waterwashable base (drug in the oil phase) and hydrophilic base (drug in the oil phase) were studied by applying the ointments on rabbit's skin. It was observed that the bioavailability of Naproxen from the hydrophilic base was slightly greater than that from the water-washable base, and that DMSO had no effect in enhancing the in-vivo release of Naproxen from the ointments evaluated. Using the in-vivo data, the absorption and elimination rate constants, the half-life and AUC were calculated.  相似文献   

15.
Abstract

The in- vitro release of Naproxen from various ointment bases, including a water-washable base with the drug in the water phase (I) and the drug in the oil phase (II), a hydrophilic base with the drug in the water phase (III), and the drug in the oil phase (IV), and an anhydrous ointment (V), a gel (VI) and a modified University of California (U.C.H.) base (VII) were studied. In addition, the effects of various additives (urea, ethanol, dimethyl sulfoxide and polyethylene glycol-400) on the release of Naproxen from formulations (I) and (II) were determined. Low concentrations of urea and ethanol in the formulations increased the release of the drug from both these bases, however, higher concentrations adversely affected the release of the drug. While dimethyl sulfoxide (DMSO) had no significant effect on the drug release, the inclusion of polyethylene glycol-400 in both bases decreased the release of Naproxen.

The percutaneous absorption of Naproxen from the waterwashable base (drug in the oil phase) and hydrophilic base (drug in the oil phase) were studied by applying the ointments on rabbit's skin. It was observed that the bioavailability of Naproxen from the hydrophilic base was slightly greater than that from the water-washable base, and that DMSO had no effect in enhancing the in-vivo release of Naproxen from the ointments evaluated. Using the in-vivo data, the absorption and elimination rate constants, the half-life and AUC were calculated.  相似文献   

16.
The in vitro release of indomethacin from 1%, 3%, and 5% indomethacin ointments and its in vivo absorption through the skin of rabbits was investigated. The in vitro release of indomethacin followed zero-order kinetics and was better from an absorption base ointment. No significant differences (F=3.047 and P=0.079 for the absorption base) and (F=2.15 and P=0.14 for the hydrophilic base) in the release rate of indomethacin in 1%, 3%, and 5% indomethacin ointments were observed. Indomethacin was most effectively absorbed from absorption ointment bases. A correlation between the in vitro release and the in vivo absorption was found; also, a correlation between the in vivo release pattern of the bases used and the in vivo data reported in the literature was observed.  相似文献   

17.
Theophylline pellets were coated with Eudragit RS 30 D in a miniature fluid-bed pan coater called MiniWiD developed recently. The dispersions were plasticized with varying amounts of triethyl citrate (TEC), dibutyl phthalate (DBP), and polyethylene glycol 6000 (PEG) and applied at different temperatures ranging from 25 to 45 °C. Theophylline release was tested by dissolution using the USP Apparatus 2 (paddle) in 0.1 N hydrochloric acid under sink conditions over 6 hours.

At a coating level of 4 % (0.7 mg/cm2) sustained-release profiles were obtained from dispersions plasticized with TEC or DBP. By reducing the amount of plasticizer from 20 to 10%, films with higher permeabilities were obtained. This effect was compensated by tempering the pellets at 50 deg;C for 24 hours. The coating temperature had little effect on the dissolution profiles of TEC-plasticized films and no effect on films with DBP.

Coatings plasticized with 20% PEG were applied at temperatures ranging from 25 to 45 °C. These films required a coating level of about 18 % (3.3 mg/cm2) to provide comparable sustained-release properties. In contrast to DBP and TEC, a strong influence of the coating temperature on the release rates was observed in which higher temperatures led to slower release rates. This behavior can be explained by the minimum film-forming temperature (MFT). Since PEG does not lower the MFT of Eudragit RS 30 D, the application of these films below the MFT of 45 °C is associated with a lower degree of film formation.  相似文献   

18.
Context: Injectable implants are biodegradable, syringeable formulations that are injected as liquids, but form a gel inside the body due to a change in pH, ions or temperature. Objective: To investigate the effect of polymer concentration, pH, ions and temperature on the gel formation of β-glucan, a natural cell-wall polysaccharide derived from barley, with particular emphasis on two-phase system formation after addition of dextran or PEG. Materials and methods: Oscillation viscometry was used to evaluate the gel character by measuring flow index (N), storage (G') and loss (G″) moduli. Two-phase systems were further characterized for hardness and syringeability using a texture analyzer. Finally, in vitro release characteristics were determined using Franz diffusion cells. Results: Oscillation viscometry revealed that only addition of dextran or PEG resulted in distinct gel formation. This was seen by a decrease in N after polymer addition. Moreover, hardness (in g) of the gels increased significantly (p?相似文献   

19.
Paromomycin (PA), a very hydrophilic antibiotic, has been tested as an alternative topical treatment against cutaneous leishmaniasis (CL). Although this treatment has shown promising results, it has not been successful in accelerating the recovery in most cases. This could be attributed to the low skin penetration of PA. Liposomal formulations usually provide sustained and enhanced drug levels in skin. The aim of this study was to prepare liposomal formulations containing PA and to investigate their potential as topical delivery systems of this antileishmanial. Large multilamellar vesicles (MLVs) were prepared by conventional solvent evaporation method. Large unilamellar vesicles (LUVs) were prepared by reverse-phase evaporation method. The lipids used were soybean phosphatidylcholine (PC) and PC:cholesterol (CH) (molar ratio 1:1). The skin permeation experiments across stripped and normal hairless mice skin were performed in modified Franz diffusion cells. The PA entrapment in LUV liposomes (20.4 ± 2.2%) was higher than that observed for MLV liposomes (7.5 ± 0.9%). Drug entrapment was 41.9 ± 6.2% and 27.2 ± 2.4% for PC and PC:CH LUV, respectively. The skin permeation was 1.55 ± 0.31%, 1.29 ± 0.40%, 0.20 ± 0.08%, and 0.50 ± 0.19% for PC LUV, PC:CH LUV, empty LUV + PA and aqueous solution, respectively. Controlled topical delivery, across stripped skin, was observed for PA entrapped in LUV liposomes.  相似文献   

20.
An application of carboxymethyl mungbean starch (CMMS) as a gelling agent in the topical pharmaceutical preparation was investigated. CMMS was prepared using specific conditions that yielded a high-viscosity product. Polymer gels and gel bases were prepared at 1–10% (wt/wt), and physicochemical studies were carried out in comparison with four standard gelling agents: carbopol 940 (CP), hydroxypropylmethyl cellulose (HPMC), methyl cellulose (MC), and sodium carboxymethyl cellulose (SCMC). Piroxicam was used as a model drug to study the drug release profile of the gel formulations. The tackless, greaseless, and transparent CMMS gels exhibited pseudoplastic behavior with thixotropy at concentrations less than 5% (wt/wt). At a concentration of 5% (wt/wt) and higher, the semisolid gels showed plastic flow characteristics. Viscosity and X-ray diffraction results indicated a good compatibility between CMMS and the acidic piroxicam. No precipitation of piroxicam or phase separation was observed during a stability test. The release rate of piroxicam from 3% (wt/wt) CMMS gel was 1,003.79 ± 105.08 μg/cm2, which was comparable with 947.66 ± 133.70 μg/cm2 obtained from a 0.5% (wt/wt) carbopol formulation. The release profiles of both formulations were consistent and remained unchanged after 2 months' storage. Viscosity played an important role in controlling the release rate of low concentration CMMS formulations by regulating the drug diffusion. At a concentration of 5% (wt/wt) CMMS and higher, the release rates of piroxicam were not significantly different. A plausible explanation based on the nature of the gelling agent was proposed. Stability and drug release profiles of CMMS and commercial gelling agents were compared. The results supported the potential use of CMMS as a new, effective gelling agent for topical gel preparation.  相似文献   

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