共查询到20条相似文献,搜索用时 57 毫秒
1.
Mamdouh M. Ghorab Heba M. Abdel-Salam Marwa A. El-Sayad Mohammed M. Mekhel 《AAPS PharmSciTech》2004,5(4):63-68
The purpose of this research was to evaluate β-cyclodextrin (β-CD) as a vehicle, either singly or in blends with lactose (spray-dried
or monohydrate), for preparing a meloxicam tablet. Aqueous solubility of meloxicam in presence of β-CD was investigated. The
tablets were prepared by direct compression and wet granulation techniques. The powder blends and the granules were evaluated
for angle of repose, bulk density, compressibility index, total porosity, and drug content. The tablets were subjected to
thickness, diameter, weight variation test, drug content, hardness, friability, disintegration time, and in vitro dissolution
studies. The effect of β-CD on the bioavailability of meloxicam was also investigated in human volunteers using a balanced
2-way crossover study. Phase-solubility studies indicated an AL-type diagram with inclusion complex of 1∶1 molar ratio. The powder blends and granules of all formulations showed satisfactory
flow properties, compressibility, and drug content. All tablet formations prepared by direct compression or wet granulation
showed acceptable mechanical properties. The dissolution rate of meloxicam was significantly enhanced by inclusion of β-CD
in the formulations up to 30%. The mean pharmacokinetic parameters (Cmax, Ke, and area under the curve [AUC]0−∞) were significantly increased in presence of β-CD. These results suggest that β-CD would facilitate the preparation of meloxicam
tablets with acceptable mechanical properties using the direct compression technique as there is no important difference between
tablets prepared by direct compression and those prepared by wet granulation. Also, β-CD is particularly useful for improving
the oral bioavailablity of meloxicam. 相似文献
2.
The aim of this work was to study the influence of β-cyclodextrin (β-CD) on the biopharmaceutic properties of diclofenac (DCF).
To this purpose the physicochemical characterization of diclofenac-β-cyclodextrin binary systems was performed both in solution
and solid state. Solid phase characterization was performed using differential scanning calorimetry (DSC), powder x-ray diffractometry
(XRD), and Fourier transform infrared spectroscopy (FTIR). Phase solubility analyses, and in vitro permeation experiments
through a synthetic membrane were performed in solution. Moreover, DCF/β-CD interactions were studied in DMSO by1H nuclear magnetic resonance (NMR) spectroscopy. The effects of different preparation methods and drug-to-β-CD molar ratios
were also evaluated. Phase solubility studies revealed 1∶1 M complexation of DCF when the freeze-drying method was used for
the preparation of the binary system. The true inclusion for the freeze-dried binary system was confirmed by1H NMR spectroscopy, DSC, powder XRD, and IR studies. The dissolution study revealed that the drug dissolution rate was improved
by the presence of CDs and the highest and promptest release was obtained with the freeze-dried binary system. Diffusion experiments
through a silicone membrane showed that DCF diffusion was higher from the saturated drug solution (control) than the freeze-dried
inclusion complexes, prepared using different DCF-β-CD molar ratios. However, the presence of the inclusion complex was able
to stabilize the system giving rise to a more regular diffusion profile.
Published: October 22, 2005 相似文献
3.
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
4.
The objective of this work is physicochemical characterization of nimesulide-cyclodextrin binary systems both in solution
and solid state and to improve the dissolution properties of nimesulide (N) via complexation with α-, β, and γ-cyclodextrins
(CDs). Detection of inclusion complexation was done in solution by means of phase solubility analysis, mass spectrometry,
and 1H nuclear magnetic resonance (1H-NMR) spectroscopic studies, and in solid state using differential scanning calorimetry (DSC), powder x-ray diffractometry
(X-RD), scanning electron microscopy (SEM), and in vitro dissolution studies. Phase solubility, mass spectrometry and 1H-NMR studies in solution revealed 1∶1 M complexation of N with all CDs. A true inclusion of N with β-CD at 1∶2 M in solid
state was confirmed by DSC, powder X-RD and SEM studies. Dissolution properties of N-CD binary systems were superior when
compared to pure N. 相似文献
5.
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
6.
This study explored the potential of β-cyclodextrin to improve the aqueous solubility and dissolution of danazol, investigated
a simple and less expensive method for preparation of a danazol-β-cyclodextrin binary system, and explored the potential application
of a danazol-β-cyclodextrin binary system as a single-dose emergency contraceptive. Phase solubility analysis indicated formation
of a first-order soluble complex with stability constant 972.03 M−1, while Job's plot affirmed 1∶1 stoichiometry. The hyperchromic shift in the UV-Vis spectrum of danazol in the presence of
β-cyclodextrin indicated solubilization capability of β-cyclodextrin for danazol. The extrinsic Cotton effect with a negative
peak at 280.7 nm confirmed the inclusion of danazol in the asymmetric locus of β-cyclodextrin.1H-nuclear magnetic resonance analysis suggested that the protons of the steroidal skeleton of danazol display favorable interactions
with the β-cyclodextrin cavity. The danazol-β-cyclodextrin binary system was prepared by kneading, solution, freeze-drying,
and milling methods. The extent of the enhancement of dissolution rate was found to be dependent on the preparation method.
Dissolution studies showed a similar relative dissolution rate (2.85) of the danazol-β-cyclodextrin binary system prepared
by the freeze-drying and milling (in the presence of 13% moisture) methods. In a mouse model, the danazol-β-cyclodextrin binary
system at 51.2 mg/kg (equivalent to a 400-mg human dose) showed 100% inhibition of implantation when given postcoitally. Moreover,
the danazol-β-cyclodextrin binary system is safe up to 2000 mg/kg in the mouse (15.52 g/70 kg human) as a single oral dose.
Thus, the danazol-β-cyclodextrin binary system could serve as a new therapeutic application: an oral emergency contraceptive
at a physiologically acceptable single dose.
Published: May 11, 2007 相似文献
7.
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
8.
The purpose of this research was to improve the solubility and therefore dissolution and bioavailability of triamterene, a
poorly water soluble diuretic, by complexation with β-cyclodextrin. Triamterene has been reported to show low bioavailability
after oral administration, with wide intersubject variation. This study presents the formulation of solid dispersions of triamterene
with β-cyclodextrin—by cogrinding, kneading, and coevaporation, using low pH conditions—and their characterizations, evaluation
of improvement in dissolution profiles, and in vivo advantage. Phase solubility studies indicated complex with possible stoichiometry
of 1∶1 and a stability constant of 167.67M−1. The solid dispersions were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance, x-ray diffraction,
and differential scanning calorimetry studies. The characterization studies confirmed inclusion of the phenyl ring of triamterene
within the nonpolar cavity of β-cyclodextrin in the coevaporate. Remarkable improvement in in vitro drug release profiles
in 0.1 N HCl and pH 6.8 phosphate buffer was observed with all dispersions, especially the coevaporate. The coevaporate, when
administered orally in rats, also exhibited improved in vivo activity, as measured by net sodium ion excretion, as compared
with triamterene powder. Thus, coevaporation of the drug and β-cyclodextrin from acidified alcohol provide the optimum condition
for inclusion complexation to give a binary system with remarkable improvement in in vitro drug release profile and in vivo
performance. 相似文献
9.
The aim of the present work was to improve the solubility and dissolution profile of Irbesartan (IRB), a poorly water-soluble
drug by formation of inclusion complex with β-cyclodextrin (βCD). Phase solubility studies revealed increase in solubility
of the drug upon cyclodextrin addition, showing AL—type of graph with slope less than one indicating formation of 1:1 stoichiometry inclusion complex. The stability constant
(K
s) was found to be 104.39 M−1. IRB–βCD binary systems were prepared by cogrinding, kneading using alcohol, kneading using aqueous alcohol, and coevaporation
methods. Characterization of the binary systems were carried out by differential scanning calorimetry, Fourier transform infrared
spectroscopy, scanning electron microscopy, X-ray diffraction, and proton nuclear magnetic resonance. The dissolution profiles
of inclusion complexes were determined and compared with those of IRB alone and physical mixture. Among the various methods,
coevaporation was the best in which the solubility was increased and dissolution rate of the drug was the highest. The study
indicated the usefulness of cyclodextrin technology to overcome the solubility problem of IRB. 相似文献
10.
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
11.
Gazzi Shanker Chegonda K. Kumar Chandra Sekhara Rao Gonugunta B. Vijaya Kumar Prabhakar Reddy Veerareddy 《AAPS PharmSciTech》2009,10(2):530-539
The study aim was concerned with formulation and evaluation of bioadhesive buccal drug delivery of tizanidine hydrochloride
tablets, which is extensively metabolized by liver. The tablets were prepared by direct compression using bioadhesive polymers
such as hydroxylpropyl methylcellulose K4M, sodium carboxymethyl cellulose alone, and a combination of these two polymers.
In order to improve the permeation of drug, different permeation enhancers like beta-cyclodextrin (β-CD), hydroxylpropyl beta-cyclodextrin
(HP-β-CD), and sodium deoxycholate (SDC) were added to the formulations. The β-CD and HP-β-CD were taken in 1:1 molar ratio
to drug in formulations. Bioadhesion strength, ex vivo residence time, swelling, and in vitro dissolution studies and ex vivo permeation studies were performed. In vitro release of optimized bioadhesive buccal tablet was found to be non-Fickian. SDC was taken in 1%, 2%, and 3% w/w of the total tablet weight. Stability studies in natural saliva indicated that optimized formulation has good stability in
human saliva. In vivo mucoadhesive behavior of optimized formulation was performed in five healthy male human volunteers and subjective parameters
were evaluated. 相似文献
12.
Marcílio S. S. Cunha-Filho Bruno Dacunha-Marinho Juan J. Torres-Labandeira Ramón Martínez-Pacheco Mariana Landin 《AAPS PharmSciTech》2007,8(3):E68-E77
The purpose of this research was to explore the utility of β cyclodextrin (βCD) and β cyclodextrin derivatives (hydroxypropyl-β-cyclodextrin
[HPβCD], sulfobutylether-β-CD [SB\CD], and a randomly methylated-β-CD [RMβCD]) to form inclusion complexes with the antitumoral
drug, β-lapachone (βLAP), in order to overcome the problem of its poor water solubility. RMβCD presented the highest efficiency
for βLAP solubilization and was selected to develop solid-state binary systems. Differential scanning calorimetry (DSC), X-ray
powder diffractometry (XRPD), Fourier transform infrared (FTIR) and optical and scanning electron microscopy results suggest
the formation of inclusion complexes by both freeze-drying and kneading techniques with a dramatic improvement in drug dissolution
efficiency at 20-minute dissolution efficiency (DE20-minute 67.15% and 88.22%, respectively) against the drug (DE20-minute 27.11%) or the βCD/drug physical mixture (DE20-minute 27.22%). However, the kneading method gives a highly crystalline material that together with the adequate drug dissolution
profile make it the best procedure in obtaining inclusion complexes of RMβCD/βLAP convenient for different applications of
βLAP.
Published: July 27, 2007 相似文献
13.
The purpose of this study was to improve dissolution behavior of poorly water-soluble drugs by application of cyclodextrin
in extrusion processes, which were melt extrusion process and wet extrusion process. Indomethacin (IM) was employed as a model
drug. Extrudates containing IM and 2-hydroxypropyl-β-cyclodextrin (HP-β-CyD) in 1:1 w/w ratio were manufactured by both melt extrusion process and wet extrusion process. In vitro drug release properties of IM from extrudates and physiochemical properties of extrudates were investigated. The dissolution
rates of IM from extrudates manufactured by melt extrusion and wet extrusion with HP-β-CyD were significantly higher than
that of the physical mixture of IM and HP-β-CyD. In extrudate manufactured by melt extrusion, γ-form of IM changed to amorphous
completely during melt extrusion due to heating above melting point of IM. On the other hand, in extrudate manufactured by
wet extrusion, γ-form of IM changed to amorphous partially due to interaction between IM and HP-β-CyD and mechanical agitating
force during process. Application of HP-β-CyD in extrusion process is useful for the enhancement of dissolution rate for poorly
water-soluble drugs. 相似文献
14.
The aim of the present study was to investigate and compare granule and tablet properties of granules prepared by wet granulation
in a rotary processor or a conventional fluid bed. For this purpose the working range of selected process variables was determined
and a factorial study with 3 factors (equipment type, filler type, and liquid addition rate) and 1 covariate (fluidizing air
flow rate) was performed. Two grades of calcium carbonate with different size and shape characteristics were applied, and
the liquid addition and fluidizing air flow rates were investigated in the widest possible range. Dry mixtures of microcrystalline
cellulose, polyvinyl povidone, calcium carbonate, and riboflavin, in a 10∶5∶84∶1 ratio, were granulated in both types of equipment.
The granulation end point was determined manually in the fluid bed and by torque measurements in the rotary processor. The
filler type had a more pronounced effect on granular properties in the fluid bed, but the rotary processor showed a higher
dependency on the investigated process variables. The rotary processor gave rise to more dense granules with better flow properties,
but the fluid bed granules had slightly better compressional properties. Furthermore, the distribution of a low-dose drug
was found to be more homogeneous in the rotary processor granules and tablets. Generally, wet granulation in a rotary processor
was found to be a good alternative to conventional fluid bed granulation, especially when cohesive powders with poor flow
properties or formulations with low drug content are to be granulated by a fluidizing air technique.
Published: March 10, 2006 相似文献
15.
Michikatsu Sato Machiko Watanabe Hiroto Nagano Yoshiaki Yagi 《Biotechnology letters》1994,16(7):703-708
A simple and specific recovery method for α-cyclodextrin (α-CD) was developed by employing co-digestion of CD reaction mixtures
with CGTase fromBacillus ohbensis and α-glucosidase. The combination of CGTase fromB. ohbensis and α-glucosidase, such as α-amylase, β-amylase, or glucoamylase was examined for the selective degradation of β-and γ-CD
in the CD reaction mixture formed by CGTase fromB. macerans. The co-digestion of the CD mixture with Taka-amylase and the CGTase resulted in α-CD and maltodextrins, the combination
with β-amylase resulted in α-CD and maltose, and that with glucoamylase resulted in α-CD and glucose. The conditions of selective
degradation of β- and γ-CD by co-digestion with the CGTase and glucoamylase were optimized as follows: the incubation pH,
5.5; incubation temperature, 50°C; CGTase concentration, 15 u/g of substrate; glucoamylase, 10 u/g of substrate; substrate
concentration, 10% (w/v); the incubation time was fixed for 18 hr from the stand point of operation convenience.
Most part of the content was presented in poster session at the 7th International Cyclodextrin Symposium, Tokyo, April 1994. 相似文献
16.
The objective of the present study was to develop once-daily sustained-release matrix tablets of nicorandil, a novel potassium
channel opener used in cardiovascular diseases. The tablets were prepared by the wet granulation method. Ethanolic solutions
of ethylcellulose (EC), Eudragit RL-100, Eudragit RS-100, and polyvinylpyrrolidone were used as granulating agents along with
hydrophilic matrix materials like hydroxypropyl methylcellulose (HPMC), sodium carboxymethylcellulose, and sodium alginate.
The granules were evaluated for angle of repose, bulk density, compressibility index, total porosity, and drug content. The
tablets were subjected to thickness, diameter, weight variation test, drug content, hardness, friability, and in vitro release
studies. The granules showed satisfactory flow properties, compressibility, and drug content. All the tablet formulations
showed acceptable pharmacotechnical properties and complied with in-house specifications for tested parameters. According
to the theoretical release profile calculation, a oncedaily sustained-release formulation should release 5.92 mg of nicorandil
in 1 hour, like conventional tablets, and 3.21 mg per hour up to 24 hours. The results of dissolution studies indicated that
formulation F-I (drug-to-HPMC, 1∶4; ethanol as granulating agent) could extend the drug release up to 24 hours. In the further
formulation development process, F-IX (drug-to-HPMC, 1∶4; EC 4% wt/vol as granulating agent), the most successful formulation
of the study, exhibited satisfactory drug release in the initial hours, and the total release pattern was very close to the
theoretical release profile. All the formulations (except F-IX) exhibited diffusion-dominated drug release. The mechanism
of drug release from F-IX was diffusion coupled with erosion. 相似文献
17.
Conclusion An inclusion complex of rofecoxib and HPβ-CD was prepared successfully by the spray-drying method in a molar ratio of 1∶1.
The inclusion complex was found to have improved in vitro drug release compared with the pure drug. The solubility profile
of complexes of rofecoxib prepared using HPβ-CD as the complexing agent in a molar ratio of 1∶1 by the spray-drying method
in pH 1.2 and pH 7.4 indicated that the acid solubility of rofecoxib was enhanced considerably by formation of an inclusion
complex with HPβ-CD. The above results also clearly demonstrated a significant decrease in the gastric ulcerogenic activity
of rofecoxib through complexation with cyclodextrins. Even though the physical mixture of rofecoxib with cyclodextrins reduced
ulcer formation, it was the spray-dried complex formation approach that minimized gastric ulceration. These findings are extremely
important from a commercial point of view as the prepared complex removes a major drawback for rofecoxib in therapy.
Published: September 20, 2005 相似文献
18.
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
19.
Molecular cloning and characterization of a novel γ-CGTase from alkalophilic Bacillus sp. 总被引:1,自引:0,他引:1
Hirano K Ishihara T Ogasawara S Maeda H Abe K Nakajima T Yamagata Y 《Applied microbiology and biotechnology》2006,70(2):193-201
We found a novel cyclodextrin glucanotransferase (CGTase) from alkalophilic Bacillus sp. G-825-6. The enzyme was expressed in the culture broth by recombinant Bacillus subtilis KN2 and was purified and characterized. The enzyme named CGTase825-6 showed 95% amino acid sequence identity with a known
enzyme β-/γ-CGTase from Bacillus firmus/lentus 290-3. However, the product specificity of CGTase825-6 differed from that of β-/γ-CGTase. CGTase825-6 produced γ-cyclodextrin
(CD) as the main product, but degradation of γ-CD was observed with prolonged reaction. The product specificity of the enzyme
was positioned between γ-CGTase produced by Bacillus clarkii 7364 and B. firmus/lentus 290-3 β-/γ-CGTase. It showed that the difference of product specificity was dependent on only 28 amino acid residues in 671
residues in CGTase825-6. We compared the amino acid sequence of CGTase825-6 and those of other CGTases and constructed a protein
structure model of CGTase825-6. The comparison suggested that the diminished loop (Val138-Asp142) should provide subsite -8
for γ-CD production and that Asp142 might have an important role in product specificity. CGTase825-6 should be a useful tool
to produce γ-CD and to study the differences of producing mechanisms between γ-CD and β-CD. 相似文献
20.
The purpose of the present study was characterization of microparticles obtained by adsorption of poorly water soluble drug,
meloxicam, on a porous silicate carrier Florite RE (FLR) and development of a tablet formulation using these microparticles,
with improved drug dissolution properties. The study also reveals the use of FLR as a pharmaceutical excipient. Meloxicam
was adsorbed on the FLR in 2 proportions (1∶1 and 1∶3), by fast evaporation of solvent from drug solution containing dispersed
FLR. Drug adsorbed FLR microparticles were evaluated for surface topography, thermal analysis, X-ray diffraction properties,
infrared spectrum, residual solvent, micromeritic properties, drug content, solubility, and dissolution studies. Microparticles
showed bulk density in the range of 0.10 to 0.12 g/cm3. Dissolution of drug from microparticles containing 1∶3, drug∶FLR ratio was faster than microparticles containing 1∶1, drug∶FLR
ratio. These microparticles were used for formulating directly compressible tablets. Prepared tablets were compared with a
commercial tablet. All the prepared tablets showed acceptable mechanical properties. Disintegration time of prepared tablets
was in the range of 18 to 38 seconds, and drug dissolution was much faster in both acidic and basic medium from prepared tablets
as compared with commercial tablet. The results suggest that FLR provides a large surface area for drug adsorption and also
that a reduction in crystallinity of drug occurs. Increase in surface area and reduction in drug crystallinity result in improved
drug dissolution from microparticles.
Published: December 7, 2005 相似文献