共查询到20条相似文献,搜索用时 125 毫秒
1.
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
2.
Rui Li Peng Quan Dong-Fei Liu Fang-Di Wei Qing Zhang Qun-Wei Xu 《AAPS PharmSciTech》2009,10(4):1137-1144
The present work was aimed at the influence of ethanol on the complex formation of hydroxypropyl-β-cyclodextrin (HP-β-CD)
with oleanolic acid (OA) and ursolic acid (UA), two insoluble isomeric triterpenic acids. Phase solubility studies were carried
out to evaluate the solubilizing power of HP-β-CD, in association with ethanol, toward OA and UA. A mathematical model was
applied to explain and predict the solubility of OA and UA influenced by HP-β-CD and ethanol. The solid complexes were prepared
by evaporating the filtrate of samples which was prepared in different complexing media. The solubility of OA is much higher
than that of UA in all the tested aqueous solutions. The solubility of OA and UA can be increased over 900 and 200 times,
respectively, by forming complex with HP-β-CD. Ethanol (0.5%, v/v) can help the formation of OA-HP-β-CD complex, but is harmful to the formation of UA-HP-β-CD complex. Increasing solubility
in water can be achieved by adding ethanol into the complexing media, but the concentration of ethanol should be optimized.
The ring E of the chemical compounds has a great influence on the complexing process. 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.
The purpose of this study was to investigate the effect of cyclodextrins (CDs) on aqueous solubility, stability, and in vitro corneal permeability of delta-8-tetrahydrocannabinol (Δ8-THC). Phase solubility of Δ8-THC was studied in the presence of 2-hydroxypropyl-β-cyclodextrin (HPβCD), randomly methylated-β-cyclodextrin (RMβCD) and
sulfobutyl ether-β-cyclodextrin sodium salt (SβCD). Stability of Δ8-THC in 5% w/v aqueous CD solutions, as a function of pH, was studied following standard protocols. In vitro corneal permeation of Δ8-THC (with and without CDs) across excised rabbit cornea was also determined. Phase-solubility profile of Δ8-THC in the presence of both HPβCD and RMβCD was of the AP type, whereas, with SβCD an AL type was apparent. Aqueous solubility of Δ8-THC increased to 1.65, 2.4, and 0.64 mg/mL in the presence of 25% w/v HPβCD, RMβCD, and SβCD, respectively. Significant degradation of Δ8-THC was not observed within the study period at the pH values studied, except for at pH 1.2. Transcorneal permeation of Δ8-THC was dramatically improved in the presence of CDs. The results demonstrate that CDs significantly increase aqueous solubility,
stability, and transcorneal permeation of Δ8-THC. Thus, topical ophthalmic formulations containing Δ8-THC and modified beta CDs may show markedly improved ocular bioavailability. 相似文献
5.
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
6.
Shen Y Wang M Zhang L Ma Y Ma B Zheng Y Liu H Luo J 《Applied microbiology and biotechnology》2011,90(6):1995-2003
A comparative investigation was performed on the effects of hydroxypropyl-β-cyclodextrin (HP-β-CD) on the growth, biocatalytic
activity, and cell integrity of Arthrobacter simplex TCCC 11037 (ASP) and Mycobacterium sp. NRRL B-3683 (MSP). The addition of HP-β-CD to ASP medium improved its cell wall permeability for lipophilic compounds but significantly inhibited its growth and biocatalytic
activity. On the other hand, the addition of HP-β-CD to MSP broth had lesser effects. Atomic force microscopy scanning analysis revealed that HP-β-CD damaged the cell integrity in ASP, especially the outermost cell surface structure, but not in MSP, which remained intact, owing to the differences in their cell wall and cell membrane composition. Protein leaking and lipid
content in ASP increased with increased HP-β-CD concentration, indicating possible alterations in ASP cell membrane features caused by HP-β-CD. These alterations may also explain the slow cell growth and decreased cell ΔΨm
in ASP upon the addition of HP-β-CD. 相似文献
7.
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
8.
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
9.
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
10.
Greice S. Borghetti Ivana S. Lula Ruben D. Sinisterra Valquiria L. Bassani 《AAPS PharmSciTech》2009,10(1):235-242
The present study was designed to investigate the influence of operating conditions (temperature, stirring time, and excess
amount of quercetin) on the complexation of quercetin with β-cyclodextrin using a 23 factorial design. The highest aqueous solubility of quercetin was reached under the conditions 37°C/24 h/6 mM of quercetin.
The stoichiometric ratio (1:1) and the apparent stability constant (Ks = 230 M−1) of the quercetin/β-cyclodextrin complex were determined using phase-solubility diagrams. The semi-industrial production
of a 1:1 quercetin/β-cyclodextrin solid complex was carried out in aqueous solution followed by spray-drying. Although the
yield of the spray-drying process was adequate (77%), the solid complex presented low concentration of quercetin (0.14%, w/w) and, thus, low complexation efficiency. The enhancement of aqueous solubility of quercetin using this method was limited
to 4.6-fold in the presence of 15 mM of β-cyclodextrin. Subsequently, an inclusion complex was prepared via physical mixture
of quercetin with β-cyclodextrin (molar ratio of 1:1 and quercetin concentration of 23% (w/w)) and characterized using infrared spectroscopy, differential scanning calorimetry, nuclear magnetic resonance spectroscopy,
and scanning electron microscopy analyses. The enhancement of aqueous solubility of quercetin using this method was 2.2-fold,
similar to that found in the complex prepared in aqueous solution before the spray-drying process (2.5-fold at a molar ratio
of 1:1, i.e., 6 mM of quercetin and 6 mM of β-cyclodextrin). 相似文献
11.
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
12.
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
13.
Kratz JM Teixeira MR Ferronato K Teixeira HF Koester LS Simões CM 《AAPS PharmSciTech》2012,13(1):118-124
Thalidomide is emerging as a therapeutic agent with renewed clinical importance, presenting anti-inflammatory, immunomodulatory,
and antineoplasic properties. In this work, we studied the complexation of thalidomide with cyclodextrins as a strategy to
circumvent the poor aqueous solubility of the drug. Thalidomide–hydroxypropyl-β-cyclodextrin complexes were obtained by kneading
method and were characterized by differential scanning calorimetry, powder X-ray diffractometry, and scanning electronic microscopy.
The aqueous solubility and in vitro dissolution of thalidomide were significantly improved through the complexation. Physicochemical analysis of the complexes
in solid state revealed a decreased crystallinity of the complexed drug in comparison with free thalidomide. Thalidomide was
able to dissociate from the complexes and permeates across intestinal epithelial Caco-2 cells with a favorable high permeability
profile equivalent to that of the free drug. In summary, the present results suggest that thalidomide–hydroxypropyl-β-cyclodextrin
complexes could be regarded as a promising strategy for improving the gastrointestinal absorption of thalidomide. 相似文献
14.
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
15.
The purpose of the present investigation was to encapsulate pure prednisolone (PRD) and PRD–hydroxypropyl-β-cyclodextrin (HPβCD)
complex in cellulose-based matrix microspheres. The system simultaneously exploits complexation technique to enhance the solubility
of low-solubility drug (pure PRD) and subsequent modulation of drug release from microspheres (MIC) at a predetermined time.
The microspheres of various compositions were prepared by an oil-in-oil emulsion–solvent evaporation method. The effect of
complexation and presence of cellulose polymers on entrapment efficiency, particle size, and drug release had been investigated.
The solid-state characterization was performed by Fourier transform infrared spectroscopy, thermogravimetry, differential
scanning calorimetry, and powder X-ray diffractometry. The morphology of MIC was examined by scanning electron microscopy.
The in vitro drug release profiles from these microspheres showed the desired biphasic release behavior. After enhancing the solubility
of prednisolone by inclusion into HPβCD, the drug release was easily modified in the microsphere formulation. It was also
demonstrated that the CDs in these microspheres were able to modulate several properties such as morphology, drug loading,
and release properties. The release kinetics of prednisolone from microspheres followed quasi-Fickian and first-order release
mechanisms. In addition to this, the f
2-metric technique was used to check the equivalency of dissolution profiles of the optimized formulation before and after
stability studies, and it was found to be similar. A good outcome, matrix microspheres (coded as MIC5) containing PRD–HPβCD
complex, showed sustained release of drug (95.81%) over a period of 24 h. 相似文献
16.
Sunil Kumar Battu Michael A. Repka Sindhuri Maddineni Amar G. Chittiboyina Mitchell A. Avery Soumyajit Majumdar 《AAPS PharmSciTech》2010,11(3):1466-1475
The objective of the present research was to evaluate the physicochemical characteristics of berberine chloride and to assess the complexation of drug with 2-hydroxypropyl-β-cyclodextrin (HPβCD), a first step towards solution dosage form development. The parameters such as log P value were determined experimentally and compared with predicted values. The pH-dependent aqueous solubility and stability were investigated following standard protocols at 25°C and 37°C. Drug solubility enhancement was attempted utilizing both surfactants and cyclodextrins (CDs), and the drug/CD complexation was studied employing various techniques such as differential scanning calorimetry, Fourier transform infrared, nuclear magnetic resonance, and scanning electron microscopy. The experimental log P value suggested that the compound is fairly hydrophilic. Berberine chloride was found to be very stable up to 6 months at all pH and temperature conditions tested. Aqueous solubility of the drug was temperature dependent and exhibited highest solubility of 4.05 ± 0.09 mM in phosphate buffer (pH 7.0) at 25°C, demonstrating the effect of buffer salts on drug solubility. Decreased drug solubility was observed with increasing concentrations of ionic surfactants such as sodium lauryl sulfate and cetyl trimethyl ammonium bromide. Phase solubility studies demonstrated the formation of berberine chloride–HPβCD inclusion complex with 1:1 stoichiometry, and the aqueous solubility of the drug improved almost 4.5-fold in the presence of 20% HPβCD. The complexation efficiency values indicated that the drug has at least threefold greater affinity for hydroxypropyl-β-CD compared to randomly methylated-β-CD. The characterization techniques confirmed inclusion complex formation between berberine chloride and HPβCD and demonstrated the feasibility of developing an oral solution dosage form of the drug.KEY WORDS: berberine chloride, complexation, cyclodextrin, solubility, surfactants 相似文献
17.
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
18.
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
19.
Erem Bilensoy M. Abdur Rouf Imran Vural Murat Šen A. Atilla Hincal 《AAPS PharmSciTech》2006,7(2):E54-E60
The purpose of this study was to achieve a better therapeutic efficacy and patient compliance in the treatment for vaginitis.
Clotrimazole (1%) has been formulated in a vaginal gel using the thermosensitive polymer Pluronic F127 (20%) together with
mucoadhesive polymers such as Carbopol 934 and hydroxypropylmethylcellulose (0.2% for both). To increase its aqueous solubility.,
clotrimazole was incorporated as its inclusion complex with 1∶1 molar ratio with β-cyclodextrin. The inclusion complex was
thoroughly characterized using various techniques, including 1H NMR spectroscopy, FT IR spectrophotometry, differential scanning calorimetry, scanning electron microscopy, phase solubility
studies, and determination of stability constant (k1∶1). The gelation temperature and rheological behavior of different formulations at varying temperatures were measured. In vitro
release profiles of the gels were determined in pH 5.5 citrate buffer. It was observed that complexation with cyclodextrin
slowed down the release of clotrimazole considerably. Carbopol 934, on the other hand, was found to interact with β-cyclodextrin,
inducing precipitation. As far as rheological properties are concerned, thermosensitive in situ gelling was obtained with
formulations containing drug: cyclodextrin complex rather than with free drug. Thus, the optimum formulation for a controlled-release
thermosensitive and mucoadhesive vaginal gel was determined to be clotrimazole: β-cyclodextrin 1% with 0.2% hydroxypropylmethylcellulose
in Pluronic F127 gel (20%) providing continuous and prolonged release of active material above MIC values. 相似文献
20.
Growth of alkaliphilic Bacillus halodurans C-125 both on agar plates and in liquid culture was inhibited by methyl-β-cyclodextrin (CD). Furthermore, resting cells of
the strain were lysed by contact with methyl-β-CD higher than 10 mM. α-CD also showed lysis activity against Bacillus and related strains. The activity was not observed with Gram-negative and Gram-positive bacteria except for Bacillus strains. Fluorescence staining and scanning electron microscopy of cells revealed that methyl-β-CD disrupted cell membranes,
and consequently, the cells were lysed. This is a novel physiological property of CDs. 相似文献