Breviscapine chitosan - Preparation of alginate microcapsules and release mechanism study
Authors: Zhang Yanqing, Zhang Mingchun, Xie Jun-Bo,
Qi Qin Services \
【Abstract】 Objective To investigate the Breviscapine chitosan - Preparation of alginate microcapsules and the drug release mechanism. Methods were prepared by re-unite
Breviscapine chitosan - alginate microcapsules. Commonly used model fitting to explore the use of drug release mechanism. Findings of the microcapsule preparation process is simple, even size, containing a large quantity of drugs and drug content uniformity. Conclusion Complex Coacervation Breviscapine method is simple and calcium alginate microcapsules, drug release mechanism for the skeleton dissolution.
Key words Breviscapine; preparation process; Chitosan -
alginate microcapsules; release mechanism
Studies on the Preparation Technology and Drug Release Mechanism of Breviscapine Chitosan-alginate Microcapsules
Abstract: ObjectiveTo investigate the preparation
technology and the drug release mechanism of Breviscapine chitosan-alginate microcapsules. MethodsBreviscapine chitosan-
alginate microcapsules were prepared by coacervation technology. Model-fitting were used to study the release
mechanism of Breviscapine from the
microcapsules.ResultsPrepared Breviscapine chitosan - alginate
microcapsules has such advantages as simple technology, uniformity in diameters and drug loading. ConclusionThe preparation procedure is simple. And the release of
Breviscapine can be described as matrix erosion.
Key words: Breviscapine; Preparation technology; Chitosan-alginate microcapsules; Release mechanism
Natural polymer chitosan and sodium alginate
polysaccharide material has good biocompatibility and
biodegradability. Chitosan as a cationic polyelectrolyte, chitosan molecular chain due to a large number of primary amino, sodium alginate molecular chain of a large number of carboxyl group, so chitosan and sodium alginate can be positive and negative charge attract the formation of poly-
electrolyte membrane, thereby enhancing the stability of the microcapsules and the drug loading, and can adjust the speed of drug release [1 ~ 3]. Breviscapine from Erigeron flavonoids extracted mainly Breviscapine A element and scutellarin, which scutellarin content of 95% over the structure of scutellarin 4 ', 5,6 trihydroxyflavone 7 glucuronic acid
glycosides. Breviscapine can reduce cerebral vascular resistance and increase cerebral blood flow. The main clinical
Breviscapine for the treatment of coronary heart disease, angina pectoris, myocardial ischemic injury and cerebral thrombosis and so on. Although the clinical efficacy Breviscapine better, but poor chemical stability, bioavailability is low, a very short plasma half-life
shortcoming [4 ~ 6], limited clinical application. In order to improve its stability and bioavailability, this article was prepared by re-unite Breviscapine chitosan - alginate
microcapsules. In addition, drug release kinetics of
pharmaceutical preparations has been an important research subject, while the use of a certain drug release process known model fitting is a common method of release mechanism, so this paper to explore the commonly used model fitting drug release
Breviscapine reference substance (Chinese medicines and biological products); Breviscapine API (Yunnan Accord Hill Pharmaceutical Co., Ltd.); chitosan (deacetylation degree
90%); alginate (Shanghai Chemical Reagent subpackage Station);
anhydrous calcium chloride (Tianjin Chemical Reagent Co., Ltd. Tong Kai); other reagents were analytical pure.
Electric constant temperature water bath pot (Beijing Changfeng Instrument Company); EMS-2 type magnetic stirrer
(Tianjin aulneau Instrument Co., Ltd.); UV-2501PC UV detector
(Shimadzu implicated type clubs); 101-4 Type Electric Blast
Oven (Shanghai Jinping Instrument Co., Ltd.); syringe (Ningbo Peace syringe factory); RQ218-type ultrasonic cleaner (Kunshan Ultrasonic Instrument Co., Ltd.); RCZ-8B Drug Dissolution
Tester, Dissolution Tester Automatic Sampling device (Tianjin University Precision Instrument Factory).
2 Methods and Results
2.1 Preparation of microcapsules that take appropriate Breviscapine powder (over 100 mesh sieve) with a certain concentration of sodium alginate by mixing a certain proportion, with syringe (6-gauge needle) to draw to a certain concentration of chitosan suspension CaCl2 solution dropwise (30 drops / min), cross-linking reaction after 2 h, remove the microcapsules, leaching, and deionized water, washed three times, placed in 40 ? oven drying 24 h, which was.
2.2 Establishment of Assay
2.2.1 Weigh absorption wavelength of the choice of an appropriate reference substance Breviscapine with pH6.8 phosphate buffered saline (PBS) dissolved and diluted to a certain concentration of solution, in the 200 ~ 400 nm wavelength scanning. The results of drugs in the PBS of pH 6.8 at 336 nm at the maximum absorption. The microcapsules used in
the proportion of accessories is available by prescription diluted filtration pH 6.8 PBS at 200 ~ 400 nm wavelength scan, the results of excipients in the drug used in the maximum absorption wavelength is not absorbed, indicating that
accessories do not interfere with the drug assay.
2.2.2 Preparation of standard curve said precision set 105 ? drying to constant weight Breviscapine reference substance is about 10 mg, placed in 100 ml Liang Ping, by
using pH 6.8 PBS dissolved and diluted to the scale. Precision drawing the solution 1.0,2.0,2.5,3.0,4.0 ml, were placed in 25 ml Liang Ping, by using pH 6.8 PBS was diluted to scale, shake. In pH 6.8 PBS as control, was measured at 336 nm absorbance (A) values. A concentration (C) of the A linear
regression equation of standard curve were: C = 21.45A-0.160
(r = 0.999 9).
2.3 The drug loading and encapsulation efficiency determination Weigh Breviscapine chitosan - alginate
microcapsules suitable set mortar in grinding, precision that
amount of powder to take home 100 ml Liang Ping, by using pH 6.8 PBS solution dissolved ultrasonic 10 min, diluted to the scale, shake, put it aside, after 0.45 μm cellulose acetate
microporous membrane filtration, abandoned to the beginning of the filtrate, filtrate continued to take back. Precision drawing filtrate 2 ml added 50 ml Liangping in the home, with pH 6.8 PBS solution was diluted to scale, shaken, was measured at 336 nm wavelength absorbance A. According to the standard curve equation, find the content of drug microcapsules
calculation. And encapsulation efficiency determined by the formula. Reposted elsewhere in the paper for free download http://
Encapsulation rate (%) = amount of drug-containing
microcapsules microcapsules and media in the total drug
content × 100%
2.4 Determination of release rate
2.4.1 release conditions rotating basket method. Speed of 100 r / min, temperature (37 ? 0.5) ?, dissolution medium is
900 ml pH 6.8 PBS.
2.4.2 Determination of amount of precision that take
microcapsules placed transfer basket. The release of the above conditions, the pH 6.8 PBS for the release of media. At the scheduled time interval sampling 5 ml (adding that with the temperature of the same volume of fresh medium), immediately
with 0.45 μm microporous membrane filtration, the filtrate
added to dissolution medium taken as control, was measured at 336 nm the value of A, according to Calculating the standard curve equation corresponding to the concentration and
cumulative release percentage.
2.5 Process reproducibility study prepared by the aforementioned process conditions prescribed three groups Breviscapine chitosan - alginate microcapsules were measured encapsulation efficiency, drug loading and in vitro release of
the results shown in Table 1 and Figure 1. From Table 1 and Figure 1 we can see the entrapment efficiency, drug loading and in vitro release of a good reproducibility, and in vitro release of drug when compared with the raw material has a good
Table 13 groups microcapsule drug loading and
encapsulation efficiency (abbreviated)
Figure 1 Breviscapine chitosan - alginate microcapsules
optimize prescription drug release curve (abbreviated)
2.6 Breviscapine chitosan - alginate microcapsules
release mechanism study process conditions prescribed by the aforementioned microcapsules prepared by in vitro release results of the kinetic model with the common zero-level model,
a model, Higuchi model and Ritger -Peppas model fitting
results in Table 2. Can be seen with the various models all have a good correlation, in which First-order model and
Ritger-Peppas model is superior to the zero level and Higuchi model. According to Ritger-Peppas , the time index of items
in terms of preparations for the round ball, when n> 0.85, the drug release mechanism for the skeleton dissolution. The release curve of n in this experiment the average is 1.00, while observed, the release experiments shortly after severe corrosion on the microcapsules to release the conclusion of microencapsulated Determination skeleton have been corrosion. May be inferred that in the pH 6.8 PBS in the Breviscapine from microcapsules prepared with matrix dissolution behavior of drug release, that is, the results of skeleton dissolution.
Table 2 Breviscapine microcapsules release the model fitting results (omitted)
Drug release kinetics of pharmaceutical preparations has been an important research subject, while the use of certain
drug release process known model fitting is a common method of release mechanism. In recent years a large number of mathematical model for drug release, most of them are based on Fick's equation under the initial conditions and boundary
conditions, analytic. Summarized in the zero-level model, a
model, Higuchi model and Ritger-Peppas model. In this study,
alginate microcapsules by Breviscapine release kinetics of
drugs commonly used model fitting process, and by observing the dissolution of the microcapsules before and after the micro-structural changes two aspects of the drug release mechanism. The results showed that with the various models all have a good correlation, in which First-order model and
Ritger-Peppas model is superior to the zero level and Higuchi model, in which time entries Ritger-Peppas average index of
1.00; also observed that the , the release experiment shortly after severe corrosion on the microcapsules to release the
conclusion of microencapsulated Determination skeleton have been corrosion. May be inferred that in the pH 6.8 PBS in the Breviscapine from microcapsules prepared with matrix dissolution behavior of drug release, that is, the results of
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