共查询到20条相似文献,搜索用时 31 毫秒
1.
Sriamornsak P Asavapichayont P Nunthanid J Luangtana-Anan M Limmatvapirat S Piriyaprasarth S 《AAPS PharmSciTech》2008,9(2):571-576
The purpose of this study was to prepare wax-incorporated pectin-based emulsion gel beads using a modified emulsion-gelation
method. The waxes in pectin–olive oil mixtures containing a model drug, metronidazole, were hot-melted, homogenized and then
extruded into calcium chloride solution. The beads formed were separated, washed with distilled water and dried for 12 h.
The influence of various types and amounts of wax on floating and drug release behavior of emulsion gel beads of calcium pectinate
was investigated. The drug-loaded gel beads were found to float on simulated gastric fluid if the sufficient amount of oil
was used. Incorporation of wax into the emulsion gel beads affected the drug release. Water-soluble wax (i.e. polyethylene
glycol) increased the drug release while other water-insoluble waxes (i.e. glyceryl monostearate, stearyl alcohol, carnauba
wax, spermaceti wax and white wax) significantly retarded the drug release. Different waxes had a slight effect on the drug
release. However, the increased amount of incorporated wax in the formulations significantly sustained the drug release while
the beads remained floating. The results suggest that wax-incorporated emulsion gel beads could be used as a carrier for intragastric
floating drug delivery. 相似文献
2.
Preparation and evaluation of chitosan/carrageenan beads for controlled release of sodium diclofenac
The polyelectrolyte complex (PEC) hydrogel beads based on chitosan (CS) and carrageenan (CR) have been studied as a controlled release device to deliver sodium diclofenac (DFNa) in the simulated gastrointestinal condition. Various factors potentially influencing the drug release (ie, CS/CR proportion, DFNa content, types and amount of cross-linking agents) were also investigated. The optimal formulation was obtained with CS/CR proportion of 2/1 and 5% (wt/vol) DFNa. The controlled release of the drug from this formulation was superior to other formulations and was able to maintain the release for approximately 8 hours. Upon cross-linking with glutaric acid and glutaraldehyde, the resulting beads were found to be more efficient for prolonged drug release than their non-cross-linking counterparts. The bead cross-linked with glutaraldehyde was able to control the release of the drug over 24 hours. The difference in the drug release behavior can be attributed to the differences in ionic interaction between the oppositely charged ions and to the concentrations of the drug within the beads, which depends on the compositions of the formulation and the pH of the dissolution medium. The release of drug was controlled by the mechanism of the dissolution of DFNa in the dissolution medium and the diffusion of DFNa through the hydrogel beads. 相似文献
3.
Modified chitosan such as chitosan alpha-ketoglutaric acid (KCTS) and hydroxamated chitosan alpha-ketoglutaric acid (HKCTS) were successfully prepared. The modified chitosan were employed in the formation of drug-loaded, iron(III)-crosslinked polymeric beads. The produced polymers were characterized by IR, NMR, WXRD and DSC measurements. The resulting beads were evaluated in vitro as drug prolonging and potentially orally administered delivery system. Theophylline was used as the loaded model drug. The generated beads proved to be successful in prolonging drug release. The release kinetics was evaluated by fitting the experimental data to standard release equations (zero-, first- and Higuchi equation). The best fit was found with Higuchi model for the polymeric beads. 相似文献
4.
Spectrophotometric quantification of lactic bacteria in alginate and control of cell release with chitosan coating 总被引:3,自引:0,他引:3
Y. Zhou E. Martins A. Groboillot C. P. Champagne & R. J. Neufeld 《Journal of applied microbiology》1998,84(3):342-348
Lactococcus lactis ssp. cremoris was entrapped within a Ca-alginate matrix, and an in situ spectrophotometric method for monitoring cell population in calcium alginate beads described. The intracapsular cell population can be estimated by measuring the optical density of beads containing cells, using cell-free beads as reference, or by measuring absorbance of a liquified bead suspension. Alginate beads, and beads coated with chitosan type I, II, and I and II mixtures, were examined for cell release. Lower viscosity chitosan (type I) coatings reduced cell release by a factor of 100 from105 cfu ml−1 to 103 cfu ml−1 after 6 h of fermentation. Reuse of chitosan I coated alginate beads also showed a reduction in cell release by a factor of 100. Cell loading and initial cell growth within the beads greatly affected cell release. Reducing the initial cell release would lower the overall levels of cell release throughout the fermentation. Compared to non-immobilized cultures, a 20–40% reduction in the lactic acid production rate was observed for alginate beads and chitosan I coated alginate beads, respectively. This reduction can be compensated for by increasing the intracapsular cell loading during immobilization, or before the onset of fermentation. 相似文献
5.
Pornsak Sriamornsak Jurairat Nunthanid Kamonrak Cheewatanakornkool Somkamol Manchun 《AAPS PharmSciTech》2010,11(3):1315-1319
Drug-loaded calcium pectinate gel (CaPG) beads were prepared by either mixing, absorption, or swelling method. The effects of drug loading method as well as the drug loading factors (i.e., drug concentration, soaking time in drug solution, type of solvent) on drug content and drug release were investigated. The amount of drug uptake (i.e., drug content) into CaPG beads increased as the initial drug concentration increased and varied depending on the loading method. The in vitro release studies in 0.1 N hydrochloric acid (HCl) and pH 6.8 buffer indicated that the drug loading method affected drug release and release parameter, time for 50% of drug release (T 50). The mixing method provided a faster drug release and lower T 50 than the absorption method and swelling method, respectively. This is probably due to higher drug content in CaPG beads. The increased concentration of drug in soaking solution and soaking time resulted in higher drug content and thus faster drug release (lower in T 50 values). When using 0.1 N HCl as solvent for soaking instead of water, the drug release was slower owing to the increase in molecular tortuosity of CaPG beads. The drug release was also affected by pH of the release medium in which drug release in 0.1 N HCl was faster than in pH 6.8 buffer. 相似文献
6.
S. M. Al-Zahrani 《Bioprocess and biosystems engineering》1999,21(1):57-60
The effects of mixing, the sodium alginate concentration, and calcium chloride concentration on the release of sulphamethoxazole (model drug) impregnated in calcium alginate beads were investigated and evaluated. The release behaviour of the sulphamethoxazole from the calcium alginate beads was studied in a 0.1N HCl aqueous solution at 37v°C. The release rate of the sulphamethoxazole depends heavily on the type of mixers during the formation of the drug-alginate beads. The highest release rate was achieved when four-bladed rectangular agitator was used while the lowest release was achieved when magnetic stirrer was used. The amount of the released sulphamethoxazole varies slightly with the variation of the alginate concentration. The total release of sulphamethoxazole when 1% w/v solution of sodium alginate was used found to be 80% of the total drug content while 72% and 68% of the total drug content for 1.5% and 2% sodium alginate solutions. Three different calcium chloride concentrations were used (i.e., 5%, 10%, and 15% CaCl2). The effect of the calcium chloride concentration on the release of the sulphamethoxazole is very pronounced. 相似文献
7.
The aim of this study was to examine the effect of pellet size, pectin type, pectin concentration, and dissolution medium on the swelling and drug release behavior of spherical pellets containing theophylline and coated with 2 different calcium pectinates, using a multi-level factorial design approach. The spherical pellets were prepared by an extrusion-spheronization method and then coated with calcium pectinate using the diffusion-controlled interfacial complexation technique, which provides a defect-free and uniform coating on solid cores. Theophylline release from the pellets was slowed by the application of the coatings. The time to release 50% of the payload (ie, T50) in an acidic medium was approximately 7 minutes from uncoated small pellets and was 55 minutes after an amidated calcium pectinate coat was applied; a comparable coat on large pellets showed a T50 of 93 minutes. Drug release profiles of dry coated pellets showed a lag time (all less than 20 minutes) when the gel coat hydrated and swelled, followed by a zero-order release. It was found that the release rate was controlled by the pellet size, pectin type, pectin concentration, and dissolution medium. 相似文献
8.
Pasquale Del Gaudio Paola Russo Maria Rosaria Lauro Paolo Colombo Rita P. Aquino 《AAPS PharmSciTech》2009,10(4):1178-1185
In this paper, ketoprofen and ketoprofen lysinate were used as model drugs in order to investigate release profiles of poorly
soluble and very soluble drug from sodium alginate beads manufactured by prilling. The effect of polymer concentration, viscosity,
and drug/polymer ratio on bead micromeritics and drug release rate was studied. Ketoprofen and ketoprofen lysinate loaded
alginate beads were obtained in a very narrow dimensional range when the Cross model was used to set prilling operative conditions.
Size distribution of alginate beads in the hydrated state was strongly dependent on viscosity of drug/polymer solutions and
frequency of the vibration. The release kinetics of the drugs showed that drug release rate was related with alginate concentration
and solubility of the drug. Alginate solutions with concentration higher than 0.50% (w/w) were suitable to prepare ketoprofen gastro-resistant formulation, while for ketoprofen lysinate alginate, concentration
should be increased to 1.50% (w/w) in order to retain the drug in gastric environment. Differential scanning calorimetry thermograms and Fourier transform
infrared analyses of drug-loaded alginate beads indicated complex chemical interactions between carboxyl groups of the drug
and polymer matrix in drug-loaded beads that contribute to the differences in release profile between ketoprofen and ketoprofen
lysinate. Total release of the drugs in intestinal medium was dependent on the solubility of the drug and was achieved between
4 and 6 h. 相似文献
9.
The objective of this study was to prepare and characterize beads of Gelucire 43/01 for floating delivery of metformin hydrochloride
(MH). The beads were evaluated for particle size, surface morphology, percent drug entrapment, percent yield, differential
scanning calorimetry (DSC), in vitro floating ability, and in vitro drug release. Aging effect on storage was evaluated using hot stage microscopy (HSM), DSC, scanning electron microscopy,
and in vitro floating ability. The formed beads were sufficiently hard and spherical in shape. Photomicrographs show that the surface
was porous in nature. The average particle diameter of beads was found to be in the size range of 3.85 to 3.95 mm, and percent
entrapment was 83.07% to 86.13%. The beads demonstrated favorable in vitro floating ability. The analysis of DSC thermograms revealed no physical interaction between the lipid and the drug in the
prepared beads. Prepared formulations showed better controlled release behavior when compared with its conventional dosage
form and comparable release profile with marketed sustained release product. HSM photomicrograph showed presence of some unmelted
portion even at 43°C and completely melts on 51°C in aged sample. It was found that there was no significant effect on floating
ability of aged beads since it remains floats up to 8 h study period. Thus, it is concluded that beads of Gelucire 43/01 could
be serve as an effective carrier for highly water-soluble antihyperglycemic drugs like MH for the controlled delivery. 相似文献
10.
A series of pH-sensitive composite hydrogel beads composed of chitosan-g-poly (acrylic acid)/attapulgite/sodium alginate (CTS-g-PAA/APT/SA) was prepared as drug delivery matrices crosslinked by Ca2+ owing to the ionic gelation of SA. The structure and surface morphology of the composite hydrogel beads were characterized by FTIR and SEM, respectively. pH-sensitivity of these composite hydrogels beads and the release behaviors of drug from them were investigated. The results showed that the composite hydrogel beads had good pH-sensitivity. The cumulative release ratios of diclofenac sodium (DS) from the composite hydrogel beads were 3.76% in pH 2.1 solution and 100% in pH 6.8 solutions within 24 h, respectively. However, the cumulative release ratio of DS in pH 7.4 solution reached 100% within 2 h. The DS cumulative release ratio reduced with increasing APT content from 0 to 50 wt%. The drug release was swelling-controlled at pH 6.8. 相似文献
11.
M. Tavakol E. Vasheghani-Farahani T. Dolatabadi-Farahani S. Hashemi-Najafabadi 《Carbohydrate polymers》2009,77(2):326-330
In the present study, spherical beads were prepared from a water-soluble chitosan (N,O-carboxymethyl chitosan, NOCC) and alginate with ionic gelation method. Then, swollen calcium–alginate–NOCC beads were coated with chitosan. To prepare drug loaded beads, sulfasalazine (SA) was added to the initial aqueous polymer solution. The effect of coating, as well as drying procedure, on the swelling behavior of unloaded beads and SA release of drug loaded ones were evaluated in simulated gastrointestinal tract fluid. The rate of swelling and drug release were decreased for air-dried and coated beads in comparison with freeze-dried and uncoated ones, respectively. No burst release of drug was observed from whole tested beads. Chitosan coated beads released approximately 40% of encapsulated drug in simulated gastric and small intestine tract fluid. Based on these results, the chitosan coated alginate–NOCC hydrogel may be used as potential polymeric carrier for colon-specific delivery of sulfasalazine. 相似文献
12.
Nikolett Kállai Oliver Luhn Judit Dredán Kristóf Kovács Miléna Lengyel István Antal 《AAPS PharmSciTech》2010,11(1):383-391
The objective of the present study was to investigate the effect of the pellet core materials isomalt, sugar, and microcrystalline cellulose on the in vitro drug release kinetics of coated sustained-release pellets as well as to evaluate the influence of different ratios of polymethacrylate copolymers exhibiting different permeability characteristics on the drug release rate. For characterization of the drug release process of pellets, the effect of osmolality was studied using glucose as an osmotically active agent in the dissolution medium. The pellet cores were layered with diclofenac sodium as model drug and coated with different ratios of Eudragit® RS30D and Eudragit® RL30D (ERS and ERL; 0:1 and 0.5:0.5 and 1:0 ratio) in a fluid bed apparatus. Physical characteristics such as mechanical strength, shape, and size proved that the inert cores were adequate for further processing. The in vitro dissolution tests were performed using a USP Apparatus I (basket method). The results demonstrated that, besides the ratio of the coating polymers (ERS/ERL), the release mechanism was also influenced by the type of starter core used. Sugar- and isomalt-type pellet cores demonstrated similar drug release profiles. 相似文献
13.
Thawachinee Buranachai Nalena Praphairaksit Nongnuj Muangsin 《AAPS PharmSciTech》2010,11(3):1128-1137
This study reports on the preparation of chitosan (CS)/polyethylene glycol (PEG) hydrogel beads using sodium diclofenac (DFNa) as a model drug. Following the optimization of the polymer to drug ratio, the chitosan beads were modified by ionic crosslinking with sodium tripolyphosphate (TPP). The CS/PEG/DFNa beads obtained from a (w/w/w) ratio of 1/0.5/0.5 with crosslinking in 10% (w/v) TPP at pH 6.0 for 30 min yielded excellent DFNa encapsulation levels with over 90% loading efficiency. The dissolution profile of DFNa from CS/PEG/DFNa beads demonstrated that this formulation was able to maintain a prolonged drug release for approximately 8 h. Among the formulations tested, the CS/PEG/DFNa (1/0.5/1 (w/w/w)) beads crosslinked with a combination of TPP (10% (w/v) for 30 min) and glutaraldehyde (GD) (5% (w/v)) were able to provide minimal DFNa release in the gastric and duodenal simulated fluids (pH 1.2 and 6.8, respectively) allowing for a principally gradual drug release over 24 h in the intestinal (jejunum and ileum) simulated fluid (pH 7.4). Thus, overall the CS/PEG beads crosslinked with TPP and GD look to be a promising and novel alternative gastrointestinal drug release system. 相似文献
14.
The aim of this study was to investigate the effect of Eudragit RS 30D, talc, and verapamil hydrochloride on dissolution and mechanical properties of beads coated with "drug-layered matrices". This was accomplished with the aid of a three-factor multiple-level factorial design using percent drug release in 1 and 2 h, T(50), tensile strength, brittleness, stiffness and toughness as the responses. Beads were coated in a fluidized-bed coating unit. Surface morphology and mechanical properties were evaluated by surface profilometry and texture analysis, respectively. No cracks, flaws and fissures were observed on the surfaces. The mechanical properties were dependent on the talc/polymer ratio. The release of verapamil from the beads was influenced by matrix components. Increasing the level of both talc and Eudragit decreased the percent drug released from 67% to 4.8% and from 80.7% to 6.7% in 1 and 2 h, respectively, and increased T(50) from 0.8 to 25.7 h. It was concluded that beads could be efficiently coated with "drug-layered matrices". The release of drug, however, depends on a balance between the levels of drug, talc, and polymer, whereby desired dissolution and mechanical properties could be controlled by the talc/polymer ratio and the level of drug loading. 相似文献
15.
Preventive and therapeutic efficacies of resveratrol on several lower gastrointestinal (GI) diseases (e.g., colorectal cancer,
colitis) are well documented. To overcome the problems due to its rapid absorption and metabolism at the upper GI tract, a
delayed release formulation of resveratrol was designed to treat these lower GI diseases. The current study aimed to develop
a delayed release formulation of resveratrol as multiparticulate pectinate beads by varying different formulation parameters.
Zinc-pectinate (Zn-pectinate) beads exhibited better delayed drug release pattern than calcium-pectinate (Ca-pectinate) beads.
The effects of the formulation parameters were investigated on shape, size, Zn content, moisture content, drug encapsulation
efficiency, swelling–erosion, and resveratrol retention pattern of the formulated beads. Upon optimization of the formulation
parameters in relative to the drug release profiles, the optimized beads were further subjected to morphological, chemical
interaction, enzymatic degradation, and stability studies. Almost all prepared beads were spherical with ∼1 mm diameter and
efficiently encapsulated resveratrol. The formulation parameters revealed great influence on resveratrol retention and swelling–erosion
behavior. In most of the cases, the drug release data more appropriately fitted with zero-order equation. This study demonstrates
that the optimized Zn-pectinate beads can encapsulate very high amount of resveratrol and can be used as delayed release formulation
of resveratrol. 相似文献
16.
Kim CJ 《AAPS PharmSciTech》2005,6(3):E429-E436
The purpose of this research was to evaluate triple layer, donut-shaped tablets (TLDSTs) for extended release dosage forms.
TLDSTs were prepared by layering 3 powders sequentially after pressing them with a punch. The core tablet consisted of enteric
polymers, mainly hydroxypropyl methylcellulose acetate succinate, and the bottom and top layers were made of a water-insoluble
polymer, ethyl cellulose. Drug release kinetics were dependent on the pH of the dissolution medium and the drug properties,
such as solubility, salt forms of weak acid and weak base drugs, and drug loading. At a 10% drug loading level, all drugs,
regardless of their type or solubility, yielded the same release profiles within an acceptable level of experimental error.
As drug loading increased from 10% to 30%, the drug release rate of neutral drugs increased for all except sulfathiazole,
which retained the same kinetics as at 10% loading. HCl salts of weak base drugs had much slower release rates than did those
of neutral drugs (eg, theophylline) as drug loading increased. The release of labetalol HCl retarded as drug loading increased
from 10% to 30%. On the other hand, Na salts of weak acid drugs had much higher release rates than did those of neutral drugs
(eg, theophylline). Drug release kinetics were governed by the ionization/erosion process with slight drug diffusion, observing
no perfect straight line. A mathematical expression for drug release kinetics (erosion-controlled system) of TLDSTs is presented.
In summary, a TLDST is a good design to obtain zero-order or nearly zero-order release kinetics for a wide range of drug solubilities. 相似文献
17.
The objective of this study was to develop a multiunit sustained release dosage form of diltiazem using a natural polymer
from a completely aqueous environment. Diltiazem was complexed with resin and the resinate-loaded carboxymethyl xanthan (RCMX)
beads were prepared by interacting sodium carboxymethyl xanthan (SCMX), a derivatized xanthan gum, with Al+3 ions. The beads were evaluated for drug entrapment efficiency (DEE) and release characteristics in enzyme free simulated
gastric fluid (SGF, HCl solution, pH 1.2) and simulated intestinal fluid (SIF, USP phosphate buffer solution, pH 6.8). Increase
in gelation time from 5 to 20 min and AlCl3 concentration from 1 to 3% decreased the DEE respectively from 95 to 79% and 88.5 to 84.6%. However, increase in gum concentration
from 1.5 to 2.5% increased the DEE from 86.5 to 90.7%. The variation in DEE was related to displacement of drug from the resinate
by the gel forming Al+3 ions. While 75–82% drug was released in 2 h in SGF from various beads, 75 to 98% drug was released in 5 hour in SIF indicating
the dependence of drug release on pH of dissolution media. Although the beads maintained their initial integrity throughout
the dissolution process in both media, as evident from scanning electron microscopic studies, the faster release in SGF was
accounted for higher swelling of the beads in SGF than in SIF. When release data (up to 60%) was fitted in power law expression,
the drug release was found to be controlled by diffusion with simultaneous relaxation phenomena. 相似文献
18.
Bajerová M Krejčová K Rabišková M Muselík J Dvořáčková K Gajdziok J Masteiková R 《AAPS PharmSciTech》2011,12(4):1348-1357
The aim of this study was to develop novel hydrogel-based beads and characterize their potential to deliver and release a
drug exhibiting pH-dependent solubility into distal parts of gastrointestinal (GI) tract. Oxycellulose beads containing diclofenac
sodium as a model drug were prepared by the ionotropic external gelation technique using calcium chloride solution as the
cross-linking medium. Resulting beads were characterized in terms of particle shape and size, encapsulation efficacy, swelling
ability and in vitro drug release. Also, potential drug–polymer interactions were evaluated using Fourier transform infrared spectroscopy. The
particle size was found to be 0.92–0.96 mm for inactive (oxycellulose only) and 1.47–1.60 mm for active (oxycellulose–diclofenac
sodium) beads, respectively. In all cases, the sphericity factor was between 0.70 and 0.81 with higher values observed for
samples containing higher polymer and drug concentrations. The swelling of inactive beads was found to be strongly influenced
by the pH and composition (i.e. Na+ concentration) of the selected media (simulated gastric fluid vs. phosphate buffer pH 6.8). The encapsulation efficiency of the prepared particles ranged from 58% to 65%. Results of dissolution
tests showed that the drug loading inside of the particles influenced the rate of its release. In general, prepared particles
were able to release the drug within 12–16 h after a lag time of 4 h. Fickian diffusion was found as the predominant drug release mechanism. Thus, this novel particulate system showed
a good potential to deliver drugs specifically to the distal parts of the human GI tract. 相似文献
19.
RH Fahmy 《AAPS PharmSciTech》2012,13(3):990-1004
Multiparticulate floating drug delivery systems have proven potential as controlled-release gastroretentive drug delivery systems that avoid the "all or none" gastric emptying nature of single-unit floating dosage forms. An objective of the presence investigation was to develop calcium silicate (CaSi)/calcium alginate (Ca-Alg)/hydroxypropyl methylcellulose (HPMC) mucoadhesive-floating beads that provide time- and site-specific drug release of alfuzosin hydrochloride (Alf). Beads were prepared by simultaneous internal and external gelation method utilizing 3(2) factorial design as an experimental design; with two main factors evaluated for their influence on the prepared beads; the concentration of CaSi as floating aid (X (1)) and the percentage of HPMC as viscosity enhancer and mucoadhesive polymer (X (2)), each of them was tested in three levels. Developed formulations were evaluated for yield, entrapment efficiency, particle size, surface topography, and buoyancy. Differential scanning calorimetry, Fourier transform infrared spectroscopy, in vitro drug release, as well as in vitro mucoadhesion using rat stomach mucosal membrane were also conducted. Percentage yield and entrapment efficiency ranged from 57.03% to 78.51% and from 49.78% to 83.26%, respectively. Statistical analysis using ANOVA proved that increasing the concentration of either CaSi or HPMC significantly increased the beads yield. Both CaSi and HPMC concentrations were found to significantly affect Alf release from the beads. Additionally, higher CaSi concentration significantly increased the beads diameter while HPMC concentration showed significant positive effect on the beads mucoadhesive properties. CaSi/Ca-Alg/HPMC beads represent simple floating-mucoadhesive gastroretentive system that could be useful in chronopharmacotherapy of benign prostatic hyperplasia. 相似文献
20.
The aim of the present research work was to develop release modulated beads of losartan potassium complexed with anion exchange
resin, Duolite AP143 (cholestyramine). Chitosan was selected as a hydrophilic polymer for the formation of beads which could
sustain the release of the drug up to 12 h, along with drug resin complex (DRC). Chitosan beads were prepared using an in-liquid
curing method by ionotropic cross-linking or interpolymer linkage with sodium tripolyphosphate (TPP). The formulation of the
beads was optimized for entrapment efficiency and drug release using 32 full factorial design. The independent variables selected were DRC/chitosan and percent of TPP. The optimization model was
validated for its performance characteristics. Studies revealed that as the concentration of chitosan and TPP was increased,
entrapment efficiency and the drug release were found to increase and decrease, respectively. The swelling capacity of chitosan–TPP
beads decreased with increasing concentration of TPP. The effect of chitosan concentration and percentage of TPP solution
used for cross-linking on entrapment efficiency and drug release rate was extensively investigated. Optimized beads were subjected
to in vivo studies in Wistar albino rats to determine the mean arterial blood pressure and compared with marketed formulation. The pharmacodynamic
study demonstrates steady blood pressure control for optimized formulation as compared to fluctuated blood pressure for the
marketed formulation. 相似文献