Dhabliya Darshana, Khan Shagufta Abdul Qaiyum, Umate Minal, Raut Bhavana, Singhavi Dilesh
Institute of Pharmaceutical Education and Research, Maharashtra, India.
Turk J Pharm Sci. 2022 Aug 31;19(4):408-415. doi: 10.4274/tjps.galenos.2021.04874.
Atazanavir sulfate (AS), a Biosafety Cabinet (BCS) class II antiretroviral drug, shows dissolution rate-limited bioavailability, therefore, it is necessary to improve its solubility and oral bioavailability. The present investigation is intended to improve the aqueous solubility by developing AS-loaded nanoparticles (ASNPs). Additionally, the immediate release formulation of AS capsules has gastrointestinal side effects such as nausea and abdominal pain, cardiovascular side effect, abnormal cardiac conduction, toxic effects on kidney and liver such as nephrolithiasis, hyperbilirubinemia, and jaundice. Therefore, ASNPs were designed to release the drug slowly for 12 h, so that these side effects could be reduced.
ASNPs were prepared using gamma-cyclodextrin (γ-CD) and the crosslinker dimethyl carbonate were characterized by differential scanning calorimetry (DSC) and X-ray diffraction (XRD) to check the crystal characteristics of AS upon entrapment in NPs. Entrapment efficiency (EE), particle size, morphology, solubility, and dissolution behavior were also determined.
EE%, particle size, and zeta potential varied from 14.38 ± 0.16 to 75.97 ± 0.28%, 65.4 ± 1.25 nm to 439.6 ± 2.21 nm, and 28.3 ± 0.1 mV to 41.0 ± 0.3 mV, respectively. XRD and DSC confirmed the transformation of the crystalline AS to amorphous in NPs. There was 11.717 folds rise in AS solubility in water from NPs. The formulation having AS: γ-CD, 1:1 at 10 mg/mL, depicted 88.55 ± 0.58, 91.23 ± 0.80, and 86.8 ± 0.65% drug release in water, acid buffer, and phosphate buffer, respectively, in 12 h.
Solubility enhancement could be attributed to the decrease in crystallinity of atazanavir, when dispersed in NPs.
硫酸阿扎那韦（AS）是一种生物安全柜（BCS）II类抗逆转录病毒药物，其生物利用度受溶出速率限制，因此，有必要提高其溶解度和口服生物利用度。本研究旨在通过开发载AS纳米颗粒（ASNPs）来提高其水溶性。此外，AS胶囊的速释制剂具有胃肠道副作用，如恶心和腹痛、心血管副作用、心脏传导异常、对肾脏和肝脏的毒性作用，如肾结石、高胆红素血症和黄疸。因此，设计ASNPs使其药物缓慢释放12小时，以便减少这些副作用。
使用γ-环糊精（γ-CD）和交联剂碳酸二甲酯制备ASNPs，通过差示扫描量热法（DSC）和X射线衍射（XRD）对其进行表征，以检查AS包封于纳米颗粒后的晶体特性。还测定了包封率（EE）、粒径、形态、溶解度和溶出行为。
EE%、粒径和zeta电位分别在14.38±0.16%至75.97±0.28%、65.4±1.25nm至439.6±2.21nm和28.3±0.1mV至41.0±0.3mV之间变化。XRD和DSC证实了纳米颗粒中结晶态AS向无定形态的转变。纳米颗粒使AS在水中的溶解度提高了11.717倍。AS与γ-CD比例为1:1、浓度为10mg/mL的制剂在12小时内分别在水、酸性缓冲液和磷酸盐缓冲液中的药物释放率为88.55±0.58%、91.23±0.80%和86.8±0.65%。
溶解度的提高可归因于阿扎那韦分散于纳米颗粒中时结晶度的降低。
