共查询到20条相似文献,搜索用时 382 毫秒
1.
Improved Bioavailability of Poorly Water-Soluble Drug Curcumin in Cellulose Acetate Solid Dispersion
Curcumin (Cur), one of the most widely used natural active constituents with a great variety of beneficial biological and
pharmacological activities, is a practically water-insoluble substance with a short biologic half-life. The aim of this study
was to develop a sustained-release solid dispersion by employing water-insoluble carrier cellulose acetate for solubility
enhancement, release control, and oral bioavailability improvement of Cur. Solid dispersions were characterized by solubility,
in vitro drug release, Fourier transform infrared spectroscopy, X-ray diffractometry, and differential scanning calorimetry studies.
The in vivo performance was assessed by a pharmacokinetic study. Solid-state characterization techniques revealed the amorphous nature
of Cur in solid dispersions. Solubility/dissolution of Cur was enhanced in the formulations in comparison with pure drug.
Sustained-release profiles of Cur from the solid dispersions were ideally controlled in vitro up to 12 h. The optimized formulation provided an improved pharmacokinetic parameter (C
max = 187.03 ng/ml, t
max = 1.95 h) in rats as compared with pure drug (C
max = 87.06 ng/ml, t
max = 0.66 h). The information from this study suggests that the developed solid dispersions successfully enhanced the solubility
and sustained release of poorly water-soluble drug Cur, thus improving its oral bioavailability effectively. 相似文献
2.
The objective of present investigation was to formulate self-microemulsifying drug delivery systems (SMEDDS) of tacrolimus
(FK 506), a poorly water soluble immunosuppressant that exhibits low and erratic bioavailability. Solubility of FK 506 in
various oils, surfactants cosurfactants and buffers was determined. Phase diagrams were constructed at different ratios of
surfactant/cosurfactant (K
m
) to determine microemulsion existence region. The effect of oil content, pH of aqueous phase, dilution, and incorporation
of drug on mean globule size of resulting microemulsions was studied. The optimized SMEDDS formulation was evaluated for in vitro dissolution profile in comparison to pure drug and marketed formulation (Pangraf capsules). The in vivo immunosuppressant activity of FK 506 SMEDDS was evaluated in comparison to Pangraf capsules. Area of o/w microemulsion region in phase diagram was increased with increase in K
m
. The SMEDDS yielded microemulsion with globule size less than 25 nm which was not affected by the pH of dilution medium.
The SMEDDS was robust to dilution and did not show any phase separation and drug precipitation even after 24 h. Optimized
SMEDDS exhibited superior in vitro dissolution profile as compared to pure drug and Pangraf capsules. Furthermore, FK 506 SMEDDS exhibited significantly higher
immunosuppressant activity in mice as compared to Pangraf capsules. 相似文献
3.
Mohamed Nasr 《AAPS PharmSciTech》2010,11(1):85-89
The objectives of this research were to prepare celecoxib proniosomes and evaluate the influence of proniosomal formulation
on the oral bioavailability of the drug in human volunteers. A new proniosomal delivery system for a poorly water-soluble
drug such as celecoxib was developed and subjected to in vitro and in vivo studies. Proniosomes were prepared by sequential spraying method, which consisted of cholesterol, span 60, and dicetyl phosphate
in a molar ratio of 1:1: 0.1, respectively. The average entrapment percent of celecoxib proniosome-derived niosomes was about
95%. The prepared proniosomes showed marked enhancement in the dissolution of celecoxib as compared to pure drug powder. The
bioavailability of 200 mg single dose of both celecoxib proniosomal formulation and a conventional marketed celecoxib capsule
was studied in human volunteers. The obtained results show that the proniosomal formulation significantly improved the extent
of celecoxib absorption than conventional capsule. The mean relative bioavailability of the proniosomal formulation to the
conventional capsule was 172.06 ± 0.14%. The mean T
max for celecoxib was prolonged when given as proniosomal capsule. There was no significant difference between the values of
K
el and t
1/2 for both celecoxib preparations. In conclusion, the proniosomal oral delivery system of celecoxib with improved bioavailability
was established. 相似文献
4.
Surmounting the constraints of limited solubilization efficiency and prime requisite of antioxidant for conventional lipid
formulations, the research work explores an edge over formulation utilizing potential applicability of rice germ oil (RGO)
as a multifunctional excipient. Self-microemulsifying drug delivery system (SMEDDS) of tacrolimus (TAC) was formulated with
RGO, an indigenous source of gamma-oryzanol. Being the same biological source, RGO and rice bran oil (RBO) were compared and
it was found that RGO have more solubilization potential for TAC (2.2-fold) as well as higher antioxidant activity (8.06-fold)
than the RBO. TAC-SMEDDS was prepared using RGO/Capmul PG8 (2:3) as an oil phase, Cremophore EL as a surfactant, and Transcutol
P as a cosurfactant. The approximate particle size of TAC-SMEDDS was found to be 38 nm by dynamic light scattering and 12 nm
by small angle neutron scattering. The in vitro dissolution studies showed complete and rapid drug release in 30 min compared to a plain drug (<5%) and marketed capsule
(<50%). AUC and C
max were found to be 45.05 ± 15.64 ng h/ml and 3.91 ± 1.2 ng/ml for TAC-SMEDDS, 12.59 ± 5.54 ng h/ml and 0.48 ± 0.12 ng/ml for
plain TAC, and 30.23 ± 10.34 ng h/ml and 2.31 ± 0.68 ng/ml for marketed formulation, respectively. The improved pharmacokinetic
profile of TAC-SMEDDS is correlating to the dissolution results. Thus, gamma-oryzanol-enriched RGO acts as a potential multifunctional
excipient for lipid formulations. 相似文献
5.
Valsartan orodispersible tablets have been developed at 40-mg dose, with the intention of facilitating administration to patients
experiencing problems with swallowing and hopefully, improving its poor oral bioavailability. Work started with selecting
drug compatible excipients depending on differential scanning calorimetric analysis. A 33 full factorial design was adopted for the optimization of the tablets prepared by freeze-drying technique. The effects of
the filler type, the binder type, and the binder concentration were studied. The different tablet formulas were characterized
for their physical properties, weight variation, disintegration time, surface properties, wetting properties, and in vitro dissolution. Amongst the prepared 27 tablet formulas, formula number 6 (consisting of 4:6 valsartan:mannitol and 2% pectin)
was selected to be tested in vivo. Oral bioavailability of two 40 mg valsartan orodispersible tablets was compared to the conventional commercial tablets after
administration of a single dose to four healthy volunteers. Valsartan was monitored in plasma by high-performance liquid chromatography.
The apparent rate of absorption of valsartan from the prepared tablets (C
max = 2.879 μg/ml, t
max = 1.08 h) was significantly higher than that of the conventional tablets (C
max = 1.471 μg/ml, t
max = 2.17 h), P ≤ 0.05. The relative bioavailability calculated as the ratio of mean total area under the plasma concentration–time curve
for the orodispersible tablets relative to the conventional ones was 135%. The results of the in vivo study revealed that valsartan orodispersible tablets would be advantageous with regards to improved patient compliance, rapid
onset of action, and increase in bioavailability. 相似文献
6.
The purpose of research was to develop a mucoadhesive multiparticulate sustained drug delivery system of pravastatin sodium,
a highly water-soluble and poorly bioavailable drug, unstable at gastric pH. Mucoadhesive microparticles were formulated using
eudragit S100 and ethyl cellulose as mucoadhesive polymers. End-step modification of w/o/o double emulsion solvent diffusion
method was attempted to improve the purity of the product, that can affect the dose calculations of sustained release formulations
and hence bioavailability. Microparticles formed were discrete, free flowing, and exhibited good mucoadhesive properties.
DSC and DRS showed stable character of drug in microparticles and absence of drug polymer interaction. The drug to polymer
ratio and surfactant concentration had significant effect on mean particle size, drug release, and entrapment efficiency.
Microparticles made with drug: eudragit S100 ratio of 1:3 (F6) exhibited maximum entrapment efficiency of 72.7% and ex vivo mucoadhesion time of 4.15 h. In vitro permeation studies on goat intestinal mucosa demonstrated a flux rate (1,243 μg/cm2/h) that was 169 times higher than the flux of pure drug. The gastric instability problem was overcome by formulating the
optimized microparticles as enteric-coated capsules that provided a sustained delivery of the highly water-soluble drug for
12 h beyond the gastric region. The release mechanism was identified as fickian diffusion (n = 0.4137) for the optimized formulation F6. Conclusively, a drug delivery system was successfully developed that showed delayed
and sustained release up to 12 h and could be potentially useful to overcome poor bioavailability problems associated with
pravastatin sodium. 相似文献
7.
《Journal of liposome research》2013,23(4):325-333
AbstractContext: The physicochemical properties of drugs such as partition coefficient play a major role in the development of lipid-based drug delivery systems. The major obstacle lies in encapsulation of a drug with low partition coefficient into these systems.Objective: The objective of this study was to design and optimize a novel lipid-based delivery system with higher loading, improved pharmacokinetics consequently enhancing the oral bioavailability of drugs with low partition coefficient like valsartan.Materials and methods: The optimized formulation consists of Capryol 90, Cremophor RH 40, and Transcutol HP. Pseudo ternary phase diagrams were used to optimize the components and their concentrations in the formulation. Dissolution studies of the selected formulations were compared with plain drug and marketed product at three pH conditions (pH 1.2, 4.5 and 6.8). Pharmacokinetic parameters of optimized formulations were determined in Wistar rats and compared with that of plain drug.Results and discussion: The optimized formulation with a mean particle size of 50?nm showed significant improvement (p?<?0.05) in dissolution rate with pH independence compared to plain drug and marketed product. The in vivo studies in Wistar rats revealed about 2.30- and 1.68-fold increase in the oral bioavailability and Cmax of valsartan from lipid-based formulation compared to plain drug.Conclusion: The engineered formulation strategy by type IV lipid-based formulations can be successfully exploited to improve the dissolution rate and oral deliverability of drugs like valsartan. 相似文献
8.
The purpose of the present study was to prepare intranasal delivery system of sildenafil citrate and estimate its relative
bioavailability after nasal administration in rabbits to attain rapid onset of action with good efficacy at lower doses. Sildenafil
citrate saturated solubility was determined in different solvents, cosolvents, and microemulsion systems. For nasal application,
sildenafil citrate was formulated in two different systems: the first was a cosolvent system (S3) of benzyl alcohol/ethanol/water/Transcutol/taurodeoxy
cholate/Tween 20 (0.5:16.8:47.7:15.9:1:18.1% w/w). The second was a microemulsion system (ME6) containing Oleic acid: Labrasol/Transcutol/water (8.33:33.3:16.66:41.66% w/w). The prepared systems were characterized in relation to their clarity, particle size, viscosity, pH, and nasal ciliotoxicity.
In vivo pharmacokinetic performance of the selected system ME6 (with no nasal ciliotoxicity) was evaluated in a group of six rabbits
in a randomized crossover study and compared to the marketed oral tablets. The targeted solubility (>20 mg/ml) of sildenafil
citrate was achieved with cosolvent systems S1, S3, and S5 and with microemulsion systems ME3–ME6. The saturated solubility
of sildenafil citrate in cosolvent system S3 and microemulsion system ME6 were 22.98 ± 1.26 and 23.79 ± 1.16 mg/ml, respectively.
Microemulsion formulation ME6 showed shorter t
max (0.75 h) and higher AUC(0-∞) (1,412.42 ng h/ml) compared to the oral tablets which showed t
max equals 1.25 h and AUC(0-∞) of 1,251.14 ng h/ml after administration to rabbits at dose level of 5 mg/kg. The relative bioavailability was 112.89%. In
conclusion, the nasal absorption of sildenafil citrate microemulsion was found to be fast, indicating the potential of nasal
delivery instead of the conventional oral administration of such drug. 相似文献
9.
Glibenclamide (GL)-loaded microcapsules (MC) and transdermal patches (TDP) were formulated and in vitro and in vivo parameters compared to find out the best route of drug administration. The formulation TDP1 having a drug–polymer ratio 1:1
showed comparatively higher GL release and better permeation across mice skin (p < 0.05). From the comparative study, it was concluded that the transdermal system of GL produced better improvement compared
to oral microcapsule administration (p < 0.05). The transdermal system exhibited comparatively slow and continuous supply of GL at a desired rate to systemic circulation
avoiding metabolism, which improved day-to-day glycemic control in diabetic subjects. Transdermal system of GL exhibited better
control of hyperglycemia and prolonged plasma half-life by transdermal systems (9.6 ± 1.2 h) in comparison with oral microcapsule
(5.84 ± 2.1 h), indicating that the drug, when administered by transdermal systems, will remain in the body for a longer period.
From the glucose tolerance test, transdermal route effectively maintained the normoglycemic levels in contrast to the oral
group (MC1), which produced remarkable hypoglycemia ranging from −12.6 ± 2.1% to −18 ± 2.3%. The significantly high (p < 0.05) area under the curve values observed with transdermal system (1,346.2 ± 92.3 ng ml−1 h−1) also indicate increased bioavailability of the drug from these systems compared to the oral route (829.8 ± 76.4 ng ml−1 h−1). 相似文献
10.
《Saudi Journal of Biological Sciences》2023,30(9):103778
Pioglitazone (PGL) is an effective insulin sensitizer, however, side effects such as accumulation of subcutaneous fat, edema, and weight gain as well as poor oral bioavailability limit its therapeutic potential for oral delivery. Recent studies have shown that combination of both, PGL and fish oil significantly reduce fasting plasma glucose, improve insulin resistance, and mitigate pioglitazone-induced subcutaneous fat accumulation and weight gain. Nevertheless, developing an effective oral drug delivery system for administration of both medications have not been explored yet. Thus, this study aimed to develop a self-micro emulsifying drug delivery system (SMEDDS) for the simultaneous oral administration of PGL and fish oil. SMEDDS was developed using concentrated fish oil,Tween® 80, and Transcutol HP and optimized by central composite design (CCD). The reconstituted, optimized PGL-SMEDDS exhibited a globule size of 142 nm, a PDI of 0.232, and a zeta potential of −20.9 mV. The in-vitro drug release study of the PGL-SMEDDS showed a first-order model kinetic release and demonstrated remarkable 15-fold enhancement compared to PGL suspension. Additionally, following oral administration in fasting albino Wistar rats, PGL-SMEDDS exhibited 3.4-fold and 1.4-fold enhancements in the AUC0–24h compared to PGL suspension and PGL marketed product. The accelerated stability testing showed that the optimized SMEDDS formulation was stable over a three-month storage period. Taken together, our findings demonstrate that the developed fish oil-based SMEDDS for PGL could serve as effective nanoplatforms for the oral delivery of PGL, warranting future studies to explore its synergistic therapeutic potential in rats. 相似文献
11.
Ramesh Gannu Chinna Reddy Palem Shravan Kumar Yamsani Vamshi Vishnu Yamsani Madhusudan Rao Yamsani 《AAPS PharmSciTech》2010,11(2):976-985
The purpose of the present study was to develop and optimize reservoir-based transdermal therapeutic system (TTS) for buspirone
(BUSP), a low bioavailable drug. A three-factor, three-level Box–Behnken design was employed to optimize the TTS. Hydroxypropyl
methylcellulose, d-limonene and propylene glycol were varied as independent variables; cumulative amount permeated across rat abdominal skin
in 24 h, flux and lag time were selected as dependent variables. Mathematical equations and response surface plots were used
to relate the dependent and independent variables. The statistical validity of polynomials was established, and optimized
formulation factors were selected by feasibility and grid search. Validation of the optimization study with seven confirmatory
runs indicated high degree of prognostic ability of response surface methodology. BUSP-OPT (optimized formulation) showed
a flux 104.6 μg cm−2 h−1, which could meet target flux. The bioavailability studies in rabbits showed that about 2.65 times improvement (p < 0.05) in bioavailability, after transdermal administration of BUSP-OPT compared to oral solution. The ex vivo–in vivo correlation was found to have biphasic pattern and followed type A correlation. Reservoir-based TTS for BUSP was developed
and optimized using Box–Behnken statistical design and could provide an effective treatment in the management of anxiety. 相似文献
12.
Development of Lipid-Based Nanoparticles for Enhancing the Oral Bioavailability of Paclitaxel 总被引:1,自引:0,他引:1
Pandita D Ahuja A Lather V Benjamin B Dutta T Velpandian T Khar RK 《AAPS PharmSciTech》2011,12(2):712-722
The current research work investigates the potential of solid lipid nanoparticles (SLNs) in improving the oral bioavailability
of paclitaxel. Paclitaxel-loaded SLNs (PTX-SLNs) were prepared by modified solvent injection method using stearylamine as
lipid, soya lecithin and poloxamer 188 as emulsifiers. SLNs were characterized in terms of surface morphology, size and size distribution,
surface chemistry and encapsulation efficiency. Pharmacokinetics and bioavailability studies were conducted in male Swiss
albino mice after oral administration of PTX-SLNs. SLNs exhibited spherical shape with smooth surface as analyzed by transmission
electron microscopy (TEM). The mean particle size of SLNs was 96 ± 4.4 nm with a low polydispersity index of 0.162 ± 0.04
and zeta potential of 39.1 ± 0.8 mV. The drug entrapment efficiency was found to be 75.42 ± 1.5% with a loading capacity of
31.5 ± 2.1% (w/w). Paclitaxel showed a slow and sustained in vitro release profile and followed Higuchi kinetic equations. After oral administration of the PTX-SLNs, drug exposure in plasma
and tissues was ten- and twofold higher, respectively, when compared with free paclitaxel solution. PTX-SLNs produced a high
mean C
max (10,274 ng/ml) compared with that of free paclitaxel solution (3,087 ng/ml). The absorbed drug was found to be distributed
in liver, lungs, kidneys, spleen, and brain. The results suggested that PTX-SLNs dispersed in an aqueous environment are promising
novel formulations that enhanced the oral bioavailability of hydrophobic drugs, like paclitaxel and were quite safe for oral
delivery of paclitaxel as observed by in vivo toxicity studies. 相似文献
13.
The present investigation was aimed at developing cytarabine-loaded poly(lactide-coglycolide) (PLGA)-based biodegradable nanoparticles
by a modified nanoprecipitation which would have sustained release of the drug. Nine batches were prepared as per 32 factorial design to optimize volume of the co-solvent (0.22–0.37 ml) and volume of non-solvent (1.7–3.0 ml). A second 32 factorial design was used for optimization of drug: polymer ratio (1:5) and stirring time (30 min) based on the two responses,
mean particle size (125 ± 2.5 nm), and percentage entrapment efficiency (21.8 ± 2.0%) of the Cyt-PLGA nanoparticles. Optimized
formulation showed a zeta potential of −29.7 mV indicating good stability; 50% w/w of sucrose in Cyt-PLGA NP was added successfully as cryoprotectant during lyophilization for freeze-dried NPs and showed
good dispersibility with minimum increase in their mean particle sizes. The DSC thermograms concluded that in the prepared
PLGA NP, the drug was present in the amorphous phase and may have been homogeneously dispersed in the PLGA matrix. In vitro drug release from the pure drug was complete within 2 h, but was sustained up to 24 h from PLGA nanoparticles with Fickian
diffusion. Stability studies showed that the developed PLGA NPs should be stored in the freeze-dried state at 2–8°C where
they would remain stable in terms of both mean particle size and drug content for 2 months. 相似文献
14.
Pratap S. Jadon Virendra Gajbhiye Rajesh S. Jadon Kavita R. Gajbhiye Narayanan Ganesh 《AAPS PharmSciTech》2009,10(4):1186-1192
The aim of the present report was to develop nonionic surfactant vesicles (niosomes) to improve poor and variable oral bioavailability
of griseofulvin. Niosomes were prepared by using different nonionic surfactants span 20, span 40, and span 60. The lipid mixture
consisted of surfactant, cholesterol, and dicetyl phosphate in the molar ratio of 125:25:1.5, 100:50:1.5, and 75:75:1.5, respectively.
The niosomal formulations were prepared by thin film method and ether injection method. The influence of different formulation
variables such as surfactant type, surfactant concentration, and cholesterol concentration was optimized for size distribution
and entrapment efficiency for both methods. Result indicated that the niosomes prepared by thin film method with span 60 provided
higher entrapment efficiency. The niosomal formulation exhibited significantly retarded in vitro release as compared with free drug. The in vivo study revealed that the niosomal dispersion significantly improved the oral bioavailability of griseofulvin in albino rats
after a single oral dose. The maximum concentration (C
max) achieved in case of niosomal formulation was approximately double (2.98 μg/ml) as compared to free drug (1.54 μg/ml). Plasma
drug profile also suggested that the developed niosomal system also has the potential of maintaining therapeutic level of
griseofulvin for a longer period of time as compared to free griseofulvin. The niosomal formulation showed significant increase
in area under the curve0-24 (AUC; 41.56 μg/ml h) as compared to free griseofulvin (22.36 μg/ml h) reflecting sustained release characteristics. In conclusion,
the niosomal formulation could be one of the promising delivery system for griseofulvin with improved oral bioavailability
and prolonged drug release profiles. 相似文献
15.
The purpose of this work was to develop and optimize gliclazide-loaded alginate–methyl cellulose mucoadhesive microcapsules
by ionotropic gelation using central composite design. The effect of formulation parameters like polymer blend ratio and cross-linker
(CaCl2) concentration on properties of gliclazide-loaded alginate–methyl cellulose microcapsules like drug encapsulation efficiency
and drug release were optimized. The optimized microcapsules were subjected to swelling, mucoadhesive, and in vivo studies. The observed responses coincided well with the predicted values from the optimization technique. The optimized microcapsules
showed high drug encapsulation efficiency (83.57 ± 2.59% to 85.52 ± 3.07%) with low T
50% (time for 50% drug release, 5.68 ± 0.09 to 5.83 ± 0.11 h). The in vitro drug release pattern from optimized microcapsules was found to be controlled-release pattern (zero order) with case II transport
release mechanism. Particle sizes of these optimized microcapsules were 0.767 ± 0.085 to 0.937 ± 0.086 mm. These microcapsules
also exhibited good mucoadhesive properties. The in vivo studies on alloxan-induced diabetic rats indicated the significant hypoglycemic effect that was observed 12 h after oral
administration of optimized mucoadhesive microcapsules. The developed and optimized alginate–methyl cellulose microcapsules
are suitable for prolonged systemic absorption of gliclazide to maintain lower blood glucose level and improved patient compliance. 相似文献
16.
The present research work was aimed to formulate clotrimazole encapsulated Cavamax W7 composite ethosomes by injection method
for improved delivery across epidermis. 32 factorial design was used to design nine formulations (F1-F9) and compared with ethosomal formulations (F10-F12). F9 with
vesicle size of 202.8 ± 4.8 nm, highest zeta potential (−83.6 ± 0.96 mV) and %EE of 98.42 ± 0.15 was selected as optimized
composite ethosome and F12 as reference ethosomal formulation. As revealed by transmission electron microscopy F9 vesicles
were more condensed, uniformly spherical in shape than F12 vesicles. Vesicular stability studies indicated F9 to be more stable
as compared to F12. Both F9 and F12 were incorporated in carbopol 934 gel base to get G1–G8 gel formulations and evaluated
for in vitro skin permeability. Cavamax W7 composite ethosomal optimized gel (G5) showed higher in vitro percent cumulative drug permeation (88.53 ± 2.10%) in 8 h and steady state flux (J
ss) of 3.39 ± 1.45 μg/cm2/min against the J
ss of 1.57 ± 0.23 μg/cm2/min for ethosomal gel (G1) and 1.13 ± 0.06 μg/cm2/min for marketed formulation. The J
ss flux of G5 was independent of amount of drug applied/unit area of skin. In vivo confocal laser scanning microscopic study of G5 depicted uniform and deeper penetration of rhodamine B (marker) in epidermis
from Cavamax W7 composite ethosomal gel in comparison to G1. Finally, G5 demonstrated better (p < 0.05) antifungal activity against Candida albicans and Aspergillus niger than G1 thus, signifying that Cavamax W7 composite ethosomes present a superior stable and efficacious vesicular system than
ethosomal formulation for topical delivery of clotrimazole. 相似文献
17.
In the present study attempt was made for preparation of isotretinoin-hydroxypropyl β cyclodextrin (HP-β-CD) inclusion complex
and encapsulate this complex in elastic liposomes to study the effect of dual carrier approach on skin targeting of isotretinoin.
The isotretinoin HP-β-CD complex was prepared by freeze-drying method and characterized by IR spectroscopy. The drug and drug-CD
complex loaded elastic liposomal formulation were prepared and characterized in vitro, ex-vivo and in vivo for shape, size, entrapment efficiency, no. of vesicles per cubic mm, in vitro skin permeation and deposition study, photodegradation and skin toxicity assay. The transdermal flux for different vesicular
formulations was observed between 10.5 ± 0.5 to 13.9 ± 1.6 μg/cm2/h. This is about 15-21 folds higher than that obtained from drug solution (0.7 ± 0.1 μg/cm2/h) and 4-5 folds higher than obtained with drug-CD complex solution (2.7 ± 0.1 μg/cm2/h). The amount of drug deposit was found to increase significantly (p < 0.05) by cyclodextrin complexation (30.1 ± 0.1 μg). The encapsulation of this complex in elastic liposomal formulation
further increases its skin deposition (262.2 ± 21 μg). The results of skin irritation study using Draize test also showed
the significant reduction in skin irritation potential of isotretinoin elastic liposomal formulation in comparison to free
drug. The results of the present study demonstrated that isotretinoin elastic liposomal formulation possesses great potential
for skin targeting, prolonging drug release, reduction of photodegradation, reducing skin irritation and improving topical
delivery of isotretinoin. 相似文献
18.
Golam Kibria Monzurul Amin Roni Mohammad Shahriarul Absar Reza-ul Jalil 《AAPS PharmSciTech》2008,9(4):1240-1246
The present study was designed to investigate the effect of two plasticizers, i.e., triethyl citrate (TEC) and polyethylene
glycol 6000 (PEG 6000) on the in vitro release kinetics of diclofenac sodium from sustained-release pellets. Ammonio methacrylate copolymer type B (Eudragit RS
30 D) is used as the release-retarding polymer. Both plasticizers were used at 10% and 15% (w/w) of Eudragit RS 30 D. Pellets were prepared by powder layering technology and coated with Eudragit RS 30 D by air suspension
technique. Thermal properties of drug and drug-loaded beads were studied using differential scanning calorimeter (DSC). DSC
thermogram represented the identity of raw materials and exhibited no interaction or complexation between the active and excipients
used in the pelletization process. Dissolution study was performed by using USP apparatus 1. No significant difference was
observed among the physical properties of the coated pellets of different batches. When dissolution was performed as pure
drug, about 8.22% and 90% drug was dissolved at 2 h in 0.1 N HCl and at 30 min in buffer (pH 6.8), respectively. From all
formulations, the release of drug in acid media was very negligible (maximum 1.8 ± 0.08% at 2 h) but in buffer only 12% and
30% drug was released at 10 h from coated pellets containing TEC and PEG 6000, respectively, indicating that Eudragit RS 30
D significantly retards the drug release rate and that drug release was varied according to the type and amount of plasticizers
used. The amount of TEC in coating formulation significantly effected drug release (p < 0.001), but the effect of PEG 6000 was not significant. Formulations containing PEG 6000 released more drug (98.35 ± 2.35%)
than TEC (68.01 ± 1.04%) after 24 h. Different kinetic models like zero order, first order, and Higuchi were used for fitting
drug release pattern. Zero order model fitted best for diclofenac release in all formulations. Drug release mechanism was
derived with Korsmeyer equation. 相似文献
19.
Lan Wu Yanli Qiao Lina Wang Jiahua Guo Guocheng Wang Wei He Lifang Yin Jinhua Zhao 《AAPS PharmSciTech》2015,16(5):1051-1058
AJS is the code name of an untitled novel medicative compound synthesized by the Tasly Holding Group Company (Tianjin, China) based on the structure of cinnamamide, which is one of the Biopharmaceutics Classification System (BCS) class II drugs. The drug has better antidepressant effect, achieved by acting on the 5-hydroxytryptamine receptor. However, the therapeutic effects of the drug are compromised due to its poor water solubility and lower bioavailability. Herein, a self-microemulsifying drug delivery system (SMEDDS) was developed to improve its solubility and oral bioavailability. AJS-SMEDDS formulation was optimized in terms of drug solubility in the excipients, droplet size, stability, and drug precipitation using a pseudo-ternary diagram. The pharmacokinetic study was performed in rats, and the drug concentration in plasma samples was assayed using the high-performance liquid chromatography-electrospray tandem mass spectrometry (HPLC-MS/MS) method. The optimized formulation for SMEDDS has a composition of castor oil 24.5%, Labrasol 28.6%, Cremphor EL 40.8%, and Transcutol HP 2.7% (co-surfactant). No drug precipitation or phase separation was observed from the optimized formulation after 3 months of storing at 25°C. The droplet size of microemulsion formed by the optimized formulation was 26.08 ± 1.68 nm, and the zeta potential was −2.76 mV. The oral bioavailability of AJS-SMEDDS was increased by 3.4- and 35.9-fold, respectively, compared with the solid dispersion and cyclodextrin inclusion; meanwhile, the Cmax of AJS-SMEDDS was about 2- and 40-fold as great as the two controls, respectively. In summary, the present SMEDDS enhanced oral bioavailability of AJS and was a promising strategy to orally deliver the drug.KEY WORDS: bioavailability, HPLC-MS/MS, self-microemulsifying drug delivery system, solubilization, stability 相似文献
20.
Chuong MC Palugan L Su TM Busano C Lee R Di Pretoro G Shah A 《AAPS PharmSciTech》2010,11(4):1650-1661
Vitamin B3 is made up of niacin (nicotinic acid) and its amide, niacinamide. Both have equivalent vitamin activity, but only niacin
(not niacinamide) is effective in lowering elevated low-density lipoprotein cholesterol and triglyceride levels in the blood.
Administration of an extended-release (ER) oral tablet would frequently encounter food. If hydrogel is used to formulate the
matrix of a biopharmaceutical classification system I drug (high solubility and high permeability), the dosage form absorbs
water and swells.. The softened outer layer may be slashed off by food present in the stomach, thus, exposing the core tablet
more readily for water absorption and speeding up drug release from its original designed rate. This project aimed to formulate
niacin CR pellets made of hydrophobic inert matrix. After niacin was melted with excipients and cooled, the mass was extruded
and spheronized into pellets. Size distribution and flowability were determined before pellets were filled into hard gelatin
capsule. The USP dissolution study revealed that a candidate formulation of 250 mg in strength released similar amount of
niacin as its commercial reference, niacin controlled-release 500 mg tablet, in 6 h (223.9 ± 23.8 mg, n = 4 versus 259.4 ± 2.6 mg, n = 3). The differential scanning calorimetry study of the pellets in capsules stored in 40°C for 4 weeks, and the content
assay of capsules in 40°C up to 6 months suggested that niacin was stable within the innovative formulation. In vitro release from this innovative ER capsules stored at 40°C up to 4 weeks were also investigated. 相似文献