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1.
Complexation of celecoxib with hydroxypropyl β-cyclodextrin (HPβCD) in the presence and absence of 3 hydrophilic polymers—polyvinyl
pyrrolidone (PVP), hydroxypropyl methylcellulose (HPMC), and polyethylene glycol (PEG)—was investigated with an objective
of evaluating the effect of hydrophilic polymers on the complexation and solubilizing efficiencies of HPβCD and on the dissolution
rate of celecoxib from the HPβCD complexes. The phase solubility studies indicated the formation of celecoxib-HPβCD inclusion
complexes at a 1∶1M ratio in solution in both the presence and the absence of hydrophilic polymers. The complexes formed were
quite stable. Addition of hydrophilic polymers markedly enhanced the complexation and solubilizing efficiencies of HPβCD.
Solid inclusion complexes of celecoxib-HPβCD were prepared in 1∶1 and 1∶2 ratios by the kneading method, with and without
the addition of hydrophilic polymers. The solubility and dissolution rate of celecoxib were significantly improved by complexation
with HPβCD. The celecoxib-HPβCD (1∶2) inclusion complex yielded a 36.57-fold increase in the dissolution rate of celecoxib.
The addition of hydrophilic polymers also markedly enhanced the dissolution rate of celecoxib from HPβCD complexes: a 72.60-,
61.25-, and 39.15-fold increase was observed with PVP, HPMC, and PEG, respectively. Differential scanning calorimetry and
X-ray diffractometry indicated stronger drug amorphization and entrapment in HPβCD because of the combined action of HPβCD
and the hydrophilic polymers.
Published: September 29, 2006 相似文献
2.
The effect of complexation of irbesartan (IRB), a practically water-insoluble drug, with cyclodextrins in presence of different
concentrations of water-soluble polymers (PEG 4000 and PVP K-90) on the dissolution rate of the drug has been investigated.
Phase solubility studies were carried out to evaluate the solubilizing power of βCD in association with water-soluble polymers
towards IRB and to determine the apparent stability constant (K
S) of the complexes. Improvement in K
S value for ternary complexes (IRB–βCD–polymers) clearly proved the benefit on the addition of water-soluble polymer to increase
complexation efficiency. The dissolution rate of the drug from ternary systems containing PEG 4000 and PVP K-90 was higher
as compared to the binary system. An optimum increase in the dissolution rate of the drug was observed at a polymer concentration
of 5% w/w for PVP K-90 and 10% w/w for PEG 4000. DSC, FTIR, SEM, and XRD studies were carried out to characterize the complexes. 相似文献
3.
The study was designed to investigate the effect of cyclodextrins (CDs) on the solubility, dissolution rate, and bioavailability
of cilostazol by forming inclusion complexes. Natural CDs like β-CD, γ-CD, and the hydrophilic β-CD derivatives, DM-β-CD and
HP-β-CD, were used to prepare inclusion complexes with cilostazol. Phase solubility study was carried out and the stability
constants were calculated assuming a 1:1 stoichiometry. Solid cilostazol complexes were prepared by coprecipitation and kneading
methods and compared with physical mixtures of cilostazol and cyclodextrins. Prepared inclusion complexes were characterized
by Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD) studies.
In vitro dissolution study was performed using phosphate buffer pH 6.4, distilled water, and HCl buffer pH 1.2 as dissolution medium.
The optimized inclusion complex was studied for its bioavailability in rabbit and the results were compared with those of
pure cilostazol and Pletoz-50. Phase solubility study showed dramatic improvement in the solubility of drug by formation of
complexes, which was further increased by pH adjustment. The dissolution rate of cilostazol was markedly augmented by the
complexation with DM-β-CD. DSC and XRD curves showed sharp endothermic peaks indicating the reduction in the microcrystallinity
of cilostazol. Selected inclusion complex was also stable at ambient temperature up to 6 months. The in vivo study revealed that DM-β-CD increased the bioavailability of cilostazol with low variability in the absorption. Among all
cilostazol–cyclodextrins complexes, cilostazol–DM-β-CD inclusion complex (1:3) prepared by coprecipitation method showed 1.53-fold
and 4.11-fold increase in absorption along with 2.1-fold and 2.97-fold increase in dissolution rate in comparison with Pletoz-50
and pure cilostazol, respectively. 相似文献
4.
Bibi F. Choonara Yahya E. Choonara Pradeep Kumar Lisa C. du Toit Lomas K. Tomar Charu Tyagi Viness Pillay 《AAPS PharmSciTech》2015,16(4):771-786
A menthol-based solid dispersion was designed to improve the intrinsic solubility of the poorly soluble sulfamethoxazole- a class II drug molecule of Biopharmaceutics Classification System (BCS) displaying widespread antibacterial activity. Solid dispersions of menthol and sulfamethoxazole were compressed with hydroxypropyl methylcellulose (HPMC) into suitable sulfamethoxazole-loaded matrix tablets for oral drug delivery. The sulfamethoxazole-loaded solid dispersions and compressed tablets were characterized for their physicochemical and physicomechanical properties such as changes in crystallinity, melting point, molecular transitions, and textural analysis for critical analysis of their effects on the solubility and dissolution of sulfamethoxazole. The formulations were further evaluated for swelling, degradation, solubility, and in vitro drug release behavior. In vitro drug release from the sulfamethoxazole-loaded matrix tablets displayed a minimum and maximum fractional release of 0.714 and 0.970, respectively. The tablets further displayed different release rate profiles over the study periods of 12, 16, 48, and 56 h which were attributed to the varying concentrations of menthol within each formulation. Menthol was determined as a suitable hydrophilic carrier for sulfamethoxazole since it functioned as a solubilizing and release-retarding agent for improving the solubility and dissolution of sulfamethoxazole as well as controlling the rate at which it was released.KEY WORDS: crystallinity, menthol, oral solubility and dissolution, solid dispersion, sulfamethoxazole 相似文献
5.
Sateeshkumar Sathigari Gurkishan Chadha Y-H. Phillip Lee Nydeia Wright Daniel L. Parsons Vijay K. Rangari Oladiran Fasina R. Jayachandra Babu 《AAPS PharmSciTech》2009,10(1):81-87
Efavirenz (EFV) is an oral antihuman immunodeficiency virus type 1 drug with extremely poor aqueous solubility. Thus, its
gastrointestinal absorption is limited by the dissolution rate of the drug. The objective of this study was to characterize
the inclusion complexes of EFV with β-cyclodextrin (β-CD), hydroxypropyl β-CD (HPβCD), and randomly methylated β-CD (RMβCD)
to improve the solubility and dissolution of EFV. The inclusion complexation of EFV with cyclodextrins in the liquid state
was characterized by phase solubility studies. The solid-state characterization of various EFV and CD systems was performed
by X-ray diffraction, differential scanning calorimetry, and scanning electron microscopy analyses. Dissolution studies were
carried out in distilled water using US Pharmacopeia dissolution rate testing equipment. Phase solubility studies provided
an AL-type solubility diagram for β-CD and AP-type solubility diagram for HPβCD and RMβCD. The phase solubility data enabled calculating stability constants (K
s) for EFV-βCD, EFV-HPβCD, and EFV-RMβCD systems which were 288, 469, and 1,073 M−1, respectively. The physical and kneaded mixtures of EFV with CDs generally provided higher dissolution of EFV as expected.
The dissolution of EFV was substantially higher with HPβCD and RMβCD inclusion complexes prepared by the freeze drying method.
Thus, complexation with HPβCD and RMβCD could possibly improve the dissolution rate-limited absorption of EFV. 相似文献
6.
The objective of this work was to develop matrix sustained-release tablets of highly water-soluble tramadol HCl using natural
gums (xanthan [X gum] and guar [G gum]) as cost-effective, nontoxic, easily available, and suitable hydrophilic matrix systems
compared with the extensively investigated hydrophilic matrices (ie, hydroxypropyl methylcellulose [HPMC]/carboxymethyl cellulose
[CMC] with respect to in vitro drug release rate) and hydration rate of the polymers. Matrix tablets of tramadol (dose 100
mg) were produced by direct compression method. Different ratios, of 100∶0, 80∶20, 60∶40, 20∶80, 0∶100 of G gum (or X):HPMC,
X gum:G gum, and triple mixture of these polymers (G gum, X gum, HPMC) were applied. After evaluation of physical characteristics
of tablets, the dissolution test was, performed in the phosphate buffer media (pH 7.4) up to 8 hours. Tablets with only X
had the highest mean dissolution time (MDT), the least dissolution efficiency (DE8%), and released the drug following a zero-order model via swelling, diffusion, and erosion mechanisms. Guar gum alone could
not efficiently control the drug release, while X and all combinations of natural gums with HPMC could retard tramadol HCl
release. However, according to the similarity factor (f
2), pure HPMC and H8G2 were the most similar formulations to Topalgic-LP as the reference standard.
Published: March 17, 2006 相似文献
7.
The effect of concentration of hydrophilic (hydroxypropyl methylcellulose [HPMC]) and hydrophobic polymers (hydrogenated castor
oil [HCO], ethylcellulose) on the release rate of tramadol was studied. Hydrophilic matrix tablets were prepared by wet granulation
technique, while hydrophobic (wax) matrix tablets were prepared by melt granulation technique and in vitro dissolution studies
were performed using United States Pharmacopeia (USP) apparatus type II. Hydrophobic matrix tablets resulted in sustained
in vitro drug release (>20 hours) as compared with hydrophilic matrix tablets (<14 hours). The presence of ethylcellulose
in either of the matrix systems prolonged the release rate of the drug. Tablets prepared by combination of hydrophilic and
hydrophobic polymers failed to prolong the drug release beyond 12 hours. The effect of ethylcellulose coating (Surelease)
and the presence of lactose and HPMC in the coating composition on the drug release was also investigated. Hydrophobic matrix
tablets prepared using HCO were found to be best suited for modulating the delivery of the highly water-soluble drug, tramadol
hydrochloride. 相似文献
8.
Priyanka Pandya Surendra Gattani Pankaj Jain Lokesh Khirwal Sanjay Surana 《AAPS PharmSciTech》2008,9(4):1247-1252
A number of synthesized chemical molecules suffer from low aqueous solubility problems. Enhancement of aqueous solubility,
dissolution rate, and bioavailability of drug is a very challenging task in drug development. In the present study, solubility
and dissolution of poorly aqueous soluble drug simvastatin (SIM) was enhanced using hydrophilic, low viscosity grade polymer
hydroxypropyl methylcellulose (HPMC K3LV). The co-solvent evaporation method was developed for efficient encapsulation of hydrophobic drug in polymer micelles of
HPMC K3LV. Spray drying and rotaevaporation method were applied for solvent evaporation. Co-solvent-evaporated mixture in solid state
was determined by differential scanning calorimetry (DSC), X-ray diffraction studies (XRD), scanning electron microscopy,
and Fourier-transform infrared spectroscopy. In vitro–in vivo studies were performed on co-solvent-evaporated mixture and compared with SIM. In vivo study was conducted on healthy albino rats (Wister strain), and formulations were administered by oral route. Results of
the study show the conversion of crystalline form of SIM into amorphous form. The dissolution rate was remarkably increased
in co-solvent-evaporated mixtures compared to SIM. co-solvent-evaporated mixtures showed better reduction in total cholesterol
and triglyceride levels than the SIM. The low-viscosity grade HPMC acts as a surfactant, which enhances the wetting of drug
and thus improves the solubility of drug. The co-solvent evaporation method provides good encapsulation efficiency and produces
amorphous form of SIM, which gave better solubility and dissolution than the crystalline SIM. 相似文献
9.
The effect of the concentration of hydrophilic (hydroxypropyl methylcellulose [HPMC]) and hydrophobic (hydrogenated castor
oil [HCO]) products, fillers (lactose and dibasic calcium phosphate), and buffers (sodium bicarbonate, calcium carbonate,
and sodium citrate) on naproxen release rate was studied. Matrix tablets were prepared by double compression, andIn vitro dissolution tests were performed. The dissolution results showed that an increased amount of HPMC or hydrogenated castor
oil resulted in reduced drug release. The inclusion of buffers in the HPMC matrix tablets enhanced naproxen release. For HCO
tablets, only sodium bicarbonate enhanced naproxen release. The presence of lactose on HPMC matrix tablets did not show a
significantly different result from that obtained with the formulation containing dibasic calcium phosphate as a filler. However,
for the tablets containing HCO, the presence of lactose significantly enhanced the naproxen release rate. The matrix-forming
materials in this study were suitable for use in sustained-release tablets containing naproxen. The drug release can be modulated
by adding suitable amounts of diluents and buffers. 相似文献
10.
Uro? Klan?ar Sa?a Baumgartner Igor Legen Polona Smrdel Nata?a Jeraj Kampu? Dejan Krajcar Bo?tjan Markun Klemen Ko?evar 《AAPS PharmSciTech》2015,16(2):398-406
It is challenging to achieve mechanically robust drug-release profiles from hydrophilic matrices containing a high dose of a drug with good solubility. However, a mechanically robust drug release over prolonged period of time can be achieved, especially if the viscosity and amount of the polymer is sufficiently high, above the “threshold values.” The goal of this research was to determine the hydroxypropyl cellulose (HPC) and hydroxypropyl methylcellulose (HPMC) polymer threshold amount that would enable robust drug release from matrix tablets containing a high dose of levetiracetam as a class I model drug according to the Biopharmaceutical Classification System (BCS). For this purpose, formulations containing HPC or HPMC of similar viscosity range, but in different amounts, were prepared. Based on the dissolution results, two final formulations were selected for additional in vitro and in vivo evaluation to confirm the robustness and to show bioequivalence. Tablets were exposed to various stress conditions in vitro with the use of different mechanically stress-inducing dissolution methods. The in vitro results were compared with in vivo results obtained from fasted and fed bioequivalence studies. Under both conditions, the formulations were bioequivalent and food had a negligible influence on the pharmacokinetic parameters Cmax and area under the curve (AUC). It was concluded that the drug release from both selected formulations is mechanically robust and that HPC and HPMC polymers with intrinsic viscosities above 9 dL/g and in quantities above 30% enable good mechanical resistance, which ensures bioequivalence. In addition, HPC matrices were found to be more mechanically robust compared to HPMC.KEY WORDS: HPC, HPMC, matrix tablets, mechanically robust dissolution, threshold amount 相似文献
11.
The inclusion complexation behavior of azadirachtin with several cyclodextrins and their methylated derivatives has been investigated in both solution and the solid state by means of XRD, TG-DTA, DSC, NMR, and UV-vis spectroscopy. The results show that the water solubility of azadirachtin was obviously increased after resulting inclusion complex with cyclodextrins. Typically, beta-cyclodextrin (beta-CD), dimethyl-beta-cyclodextrin (DMbetaCD), permethyl-beta-cyclodextrin (TMbetaCD), and hydroxypropyl-beta-cyclodextrin (HPbetaCD) are found to be able to solubilize azadirachtin to high levels up to 2.7, 1.3, 3.5, and 1.6 mg/mL (calculated as azadirachtin), respectively. This satisfactory water solubility and high thermal stability of the cyclodextrin-azadirachtin complexes, will be potentially useful for their application as herbal medicine or healthcare products. 相似文献
12.
Polymethoxyflavones (PMF) isolated from citrus peel have potent anti-cancer activity, however their utilization as functional ingredients in foods is currently limited because of their high melting point and poor water-solubility. The influence of oil type and concentration, hydrophilic polymer addition, and simulated intestinal conditions on PMF (5-hydroxytangeretin) solubility in solutions and nanoemulsions was examined. The saturation concentration of PMF in water was relatively low (0.93???M), but could be increased appreciably by adding certain hydrophilic polymers: polyethylene glycol (PEG) and ??-cyclodextrin (CD) were ineffective at increasing solubility, but poly(vinyl alcohol) (PVA) and hydroxypropyl methylcellulose (HPMC) greatly enhanced solubility (e.g., > 6???M for 0.5?% polymer). PMF was more soluble in medium chain triglycerides (MCT, 6.1?mM) than long chain triglycerides (LCT, 4.2?mM). The encapsulation efficiency of PMF in oil-in-water nanoemulsions was higher when MCT was used as the oil phase rather than LCT, and could be increased by increasing the oil droplet content. The solubility of PMF in simulated small intestinal fluids was increased by solubilization in bile micelles and mixed micelles formed during lipid digestion. These results have important implications for the development of functional foods fortified with bioactive hydrophobic components aimed at improving human health and wellness. 相似文献
13.
The present work investigates the effect of complexation with hydroxypropyl-beta-cyclodextrin (HPBCD) and 2-O-methyl-beta-cyclodextrin (2-O-MBCD), on voriconazole solubility, dissolution rate and chemical stability. Drug–cyclodextrin complexes were prepared as aqueous solutions, which were spray-dried, and their properties were compared to wet ground samples and physical mixtures. DSC analysis revealed absence of crystalline voriconazole from spray-dried complexes. FTIR spectroscopy indicated changes in the H-bonding network of the hydroxyl groups of cyclodextrin following drug inclusion. Dissolution rate of voriconazole was significantly higher from spray-dried complexes with either cyclodextrin in comparison with free drug, physical mixtures, or wet ground mixtures. However, two degradation impurities were found in aged samples, with slightly higher impurity level with HPBCD. Performed solubility studies suggested that 2-O-MBCD is more efficient solubilizer. Molecular docking simulations showed a difference in the 1:1 binding affinities and sites, with HPBCD surprisingly forming complexes of much lower energy, thus suggesting a multiple rather than a 1:1 complexation. 相似文献
14.
The main objective of this work was to increase the solubility of sulfadiazine by formation of inclusion complexes with β-cyclodextrin, and methyl-β-cyclodextrin. The apparent stability constants have been determined by phase solubility studies in water and buffer solutions of pH values of 2 and 8. The stoichiometry of all complexes was found to be 1:1 but different relative affinities were found for each cyclodextrin. It was possible to obtain a greater overall solubility by using a combined approach of pH adjustment and complexation with cyclodextrins. Guest-host interactions have been investigated using nuclear magnetic resonance. Complexes were prepared in solid state by different methods and were characterized using differential scanning calorimetry, thermogravimetric analysis, Fourier-transform infrared spectroscopy, X-ray diffractometry and scanning electron microscopy. The dissolution rate of the drug from the inclusion complex made by freeze-dried was much faster than this of the pure drug. 相似文献
15.
Siahi-Shadbad MR Asare-Addo K Azizian K Hassanzadeh D Nokhodchi A 《AAPS PharmSciTech》2011,12(4):1176-1182
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
16.
The studies reported in this work are aimed to elucidate the ternary inclusion complex formation of gemfibrozil (GFZ), a poorly
water-soluble drug, with β-cyclodextrin (β-CD) with the aid of auxiliary substances like different grades of povidone(s) (viz.
PVP K-29/32, PVP K-40, Plasdone S-630, and Polyplasdone XL), organic base (viz. triethanolamine), and metal ion (viz. MgCl2·6H2O), by investigating their interactions in solution and solid state. Phase solubility studies were carried out to evaluate
the solubilizing power of β-cyclodextrin, in association with various auxiliary substances, to determine the apparent stability
constant (K
C) and complexation efficiency (CE) of complexes. Improvement in K
C values for ternary complexes clearly proves the benefit of the addition of auxiliary substances to promote CE. Of all the
approaches used, the use of polymer Plasdone S-630 was found to be the most promising approach in terms of optimum CE and
K
C. GFZ–β-CD (1:1) binary and ternary systems were prepared by kneading and lyophilization methods. The ternary systems clearly
signified superiority over binary systems in terms of CE, solubility, K
C, and reduction in the formulation bulk. Optimized ternary system of GFZ–β-CD–Plasdone S-630 prepared by using lyophilization
method indicated a significant improvement in intrinsic dissolution rate when compared with ternary kneaded system. Differential
scanning calorimetry, X-ray diffraction, Fourier transform infrared, scanning electron microscopy, and proton nuclear magnetic
resonance were carried out to characterize the binary and optimized ternary complex. The results suggested the formation of
new solid phases, eliciting strong evidences of ternary inclusion complex formation between GFZ, β-CD, and Plasdone S-630,
particularly for lyophilized products. 相似文献
17.
The aim of this study was to improve the solubility and oral bioavailability of clozapine (CLZ), a poorly water-soluble drug subjected to substantial first-pass metabolism, employing cyclodextrin complexation technique. The inclusion complexes were prepared by an evaporation method. Phase solubility studies, differential scanning calorimetry, X-ray powder diffraction, and Fourier transform infrared spectroscopy were used to evaluate the complexation of CLZ with hydroxypropyl-β-cyclodextrin (HP-β-CD) and the formation of true inclusion complexes. Characterization and dissolution studies were carried out to evaluate the orally disintegrating tablets (ODTs) containing CLZ/HP-β-CD complexes prepared by direct compression. Finally, the bioavailability studies of the prepared ODTs were performed by oral administration to rabbits. The ODTs showed a higher in vitro dissolution rate and bioavailability compared with the commercial tablets. It is evident from the results herein that the developed ODTs provide a promising drug delivery system in drug development, owing to their excellent performance of a rapid onset of action, improved bioavailability, and good patient compliance. 相似文献
18.
Kiran Kumar Vangara Hamed Ismail Ali Dai Lu Jingbo Louise Liu Srikanth Kolluru Srinath Palakurthi 《AAPS PharmSciTech》2014,15(2):472-482
SN-38, an active metabolite of irinotecan, is up to 1,000-fold more potent than irinotecan. But the clinical use of SN-38 is limited by its extreme hydrophobicity and instability at physiological pH. To enhance solubility and stability, SN-38 was complexed with different cyclodextrins (CDs), namely, sodium sulfobutylether β-cyclodextrin (SBEβCD), hydroxypropyl β-cyclodextrin, randomly methylated β-cyclodextrin, and methyl β-cyclodextrin, and their influence on SN-38 solubility, stability, and in vitro cytotoxicity was studied against ovarian cancer cell lines (A2780 and 2008). Phase solubility studies were conducted to understand the pattern of SN-38 solubilization. SN-38-βCD complexes were characterized by differential scanning calorimetry (DSC), X-ray powder diffraction analysis (XRPD), and Fourier transform infrared (FTIR). Stability of SN-38-SBEβCD complex in pH 7.4 phosphate-buffered saline was evaluated and compared against free SN-38. Phase solubility studies revealed that SN-38 solubility increased linearly as a function of CD concentration and the linearity was characteristic of an AP-type system. Aqueous solubility of SN-38 was enhanced by about 30–1,400 times by CD complexation. DSC, XRPD, and FTIR studies confirmed the formation of inclusion complexes, and stability studies revealed that cyclodextrin complexation significantly increased the hydrolytic stability of SN-38 at physiological pH 7.4. Cytotoxicity of SN-38-SBEβCD complex was significantly higher than SN-38 and irinotecan in both A2780 and 2008 cell lines. Results suggest that SBEβCD encapsulated SN-38 deep into the cavity forming stable inclusion complex and as a result increased the solubility, stability, and cytotoxicity of SN-38. It may be concluded that preparation of inclusion complexes with SBEβCD is a suitable approach to overcome the solubility and stability problems of SN-38 for future clinical applications. 相似文献
19.
Doile MM Fortunato KA Schmücker IC Schucko SK Silva MA Rodrigues PO 《AAPS PharmSciTech》2008,9(1):314-321
Inclusion complexes between dexamethasone acetate (DMA), a poorly water soluble drug, and β-cyclodextrin (βCD) were obtained
to improve the solubility and dissolution rate of this drug. Phase-solubility profile indicated that the solubility of DMA
was significantly increased in the presence of βCD (33-fold) and was classified as AL-type, indicating the 1:1 stoichiometric inclusion complexes. Solid complexes prepared by different methods (kneading, coevaporation,
freeze drying) and physical mixture were characterized by differential scanning calorimetry, thermogravimetry, infrared absorption
and optical microscopy. Preparation methods influenced the physicochemical properties of the products. The dissolution profiles
of solid complexes were determined and compared with those DMA alone and their physical mixture, in three different mediums:
simulated gastric fluid (pH 1.2), simulated intestinal fluid (pH 7.4) and distilled water. The dissolution studies showed
that in all mediums DMA presented an incomplete dissolution even in four hours. In contrast, the complexes formed presented
a higher dissolution rate in simulated gastric fluid (SGF pH 1.2), which indicate that these have different ionization characteristics.
According to the results, the freeze–dried and kneaded products exhibited higher dissolution rates than the drug alone, in
all the mediums. 相似文献
20.
The solubilizing and absorption enhancer properties towards nimesulide (ND) of tromethamine (Tris) and polyvinylpyrrolidone
(PVP) have been investigated. Solid binary systems were prepared at various drug-polymer ratios by mixing or coprecipitation,
characterized by differential scanning calorimetry, X-ray diffractometry, and Fourier transform infrared spectroscopy, and
tested for dissolution behavior. Both carriers improved drug dissolution and their performance depended on concentration of
the hydrophilic carrier in coprecipitates. Tris was more effective than PVP, despite the amorphizing power of PVP as revealed
by solid state analyses. Complete drug amorphiztion was attained at 1∶3 (wt/wt) drug: PVP, 25% (wt/wt) ND in PVP. According
to thermal behavior of ND and Tris, ND-Tris systems present a eutectic behavior. The eutectic composition was 30% ND-70% Tris
at ∼129°C. Amorphous ND-PVP and eutectic ND-Tris mixtures showed an improvement of 5.55 and 6.6 times of drug dissolution
efficiency, respectively. In vivo experiments in mice demonstrated that administration of 60 mg/kg of drug coprecipitated
with PVP or Tris resulted, respectively, in a 50% and 94% reduction of acetic acid-induced writhings in comparison with pure
drug, which, instead, was statistically ineffective as compared with the control group. Moreover, the eutectic mixture of
ND-Tris demonstrated antiwrithing potency 1.88 times higher than amorphous ND-PVP coprecipitate. Thus, the solubilizing power,
dissolution-enhancing effect, and analgesic effect enhancer ability toward the drug make Tris particularly suitable for developing
a reduced-dose, fast-release solid oral dosage form of nimesulide.
Published: August 10, 2007 相似文献