阿奇霉素口服微球的制备及其评价
Preparation and evaluation of azithromycin-loaded microspheres for oral administration
-
摘要: 为改善阿奇霉素（AZI）苦味与服药顺应性，以乙基纤维素（EC）为载体，采用O/W乳化溶剂挥发法制备载阿奇霉素口服微球（AZI-EC MS），对其释放与掩味效果进行初步考察，并通过差式扫描量热法、红外光谱和扫描电镜表征。通过联合应用不同相对分子质量EC解决了微球突释问题，当药载质量比1∶1、混合EC（N22/T10，7∶3）为载体时，微球0.5 h累积释放量小于40%，8 h累积释放量可达90%；该微球载药量为(48.95±0.86)%，形态圆整，表面光滑。AZI味道极苦，苦味阈值浓度为9.93 μg/mL，所制备的AZI-EC MS掩味效果良好。结果表明，混合EC为载体的AZI-EC MS能够改善AZI苦味，提高患者顺应性，为AZI新制剂的研究开发奠定基础。Abstract: To mask the bitterness of azithromycin（AZI） and improve patient compliance, an AZI-loaded microsphere (AZI-EC MS) for oral administration was prepared by O/W emulsion solvent evaporation with ethylcellulose (EC) as carrier. The release profiles and taste-masking effect of AZI-EC MS were preliminarily assessed. Its physical properties and morphology were then investigated by differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM). The results indicated that the polymer weight of EC could influence the drug release behavior. With a drug polymer ratio of 1∶1 and mixed EC (N22/T10, 7∶3) as carrier, the cumulative release of AZI-EC MS at 0.5 h was less than 40% and reached 90% at 8 h; the drug loading efficiency of microspheres was (48.95 ± 0.86)% with smooth spherical morphology. The AZI bitterness threshold is 9.93 μg/mL with a strong bitter taste, which indicated a better taste masking effect. Therefore, AZI-EC MS prepared in this study can mask AZI bitterness and improve patient compliance, setting the stage for the research of new AZI preparations.
-
Keywords:
- azithromycin /
- microspheres /
- preparation /
- bitter taste threshold /
- ethylcellulose
-
-
[1] . Profiles Drug Subst Excip Relat Methodol， 2014， 39：1-40. [2] Hansen MP， Scott AM， McCullough A， et al. Adverse events in people taking macrolide antibiotics versus placebo for any indication［J］. Cochrane Database Syst Rev， 2019， 1： CD011825 .[3] Walsh J， Cram A， Woertz K， et al. Playing hide and seek with poorly tasting paediatric medicines：do not forget the excipients［J］. Adv Drug Deliv Rev， 2014， 73：14-33. [4] Lopez FL， Ernest TB， Tuleu C， et al. Formulation approaches to pediatric oral drug delivery：benefits and limitations of current platforms［J］. Expert Opin Drug Deliv， 2015， 12（11）：1727-1740. [5] Ivanovska V， Rademaker CM， van Dijk L， et al. Pediatric drug formulations：a review of challenges and progress［J］. Pediatrics， 2014， 134（2）：361-372. [6] Mistry P， Batchelor H. Evidence of acceptability of oral paediatric medicines：a review［J］. J Pharm Pharmacol， 2017， 69（4）：361-376. [7] Sun JD，Zhang ZQ，He SW，et al.Progress on novel pediatric oral solid dosage forms［J］.J China Pharm Univ（中国药科大学学报），2019，50（6）：631-640. [8] Lopez FL， Mistry P， Batchelor HK， et al. Acceptability of placebo multiparticulate formulations in children and adults［J］. Sci Rep， 2018， 8（1）：9210. [9] Gandhi R， Kaul CL， Panchagnula R. Pharmacokinetic evaluation of an azithromycin controlled release dosage form in healthy human volunteers：a single dose study［J］. Int J Pharm， 2004， 270（1/2）：1-8. [10] Curatolo W. Interdisciplinary science and the design of a single-dose antibiotic therapy［J］. Pharm Res， 2011， 28（9）：2059-2071. [11] Kharb V， Saharan VA， Dev K， et al. Formulation， evaluation and 3（2） full factorial design-based optimization of ondansetron hydrochloride incorporated taste masked microspheres［J］. Pharm Dev Technol， 2014， 19（7）：839-852. [12] Pein M， Preis M， Eckert C， et al. Taste-masking assessment of solid oral dosage forms：a critical review［J］. Int J Pharm， 2014， 465（1/2）：239-254.
计量
- 文章访问数: 245
- HTML全文浏览量: 2
- PDF下载量: 506
下载:
