Preparation and Optimization of Ibrutinib-Loaded Nanoliposomes Using Response Surface Methodology

Author:

Ashar Fareeaa,Hani UmmeORCID,Osmani Riyaz Ali M.ORCID,Kazim Syed Mohammed,Selvamuthukumar S.ORCID

Abstract

The main aim of this study was to optimize the formulation and process variables for the preparation of ibrutinib nanoliposomes and to evaluate the stability of nanoliposomes. The influence of four formulations and process parameters, namely, the phosphatidylcholine-to-cholesterol ratio (A), conc. of ibrutinib (B), sonication time (C), and stirring time (D) on the drug encapsulation efficiency (Y1) and particle size (Y2) of ibrutinib nanoliposomes were investigated by using response surface methodology. Reverse-phase evaporation was used to prepare ibrutinib nanoliposomes. Twenty-nine trial experiments were performed as per the design and the response parameters were noted. Multiple linear regression analysis was used to assess each response parameter. The effect of each factor on the response parameters was depicted using perturbation, response surface, and contour plots. A numerical optimization technique was used to estimate the optimum process parameters to obtain the desired responses. Ibrutinib nanoliposomes prepared under optimal conditions were evaluated for stability at a different temperature, pH, and sonication time. It is evident from the results that the phosphatidylcholine-to-cholesterol ratio (A) was the major factor influencing the encapsulation efficiency. All the factors were found to have noteworthy influences on particle size. A statistical evaluation provided the information about the individual and interactive effects of independent factors on the response parameters in order to obtain optimum experimental conditions that lead to preparing nanoliposomes with improved characteristics. The optimum level of the independent variables was phosphatidylcholine:cholesterol (6.76:1), ibrutinib concentration (2 mg/mL), sonication time (15.13 min), and stirring time (45 min). At optimal conditions, Y1 and Y2 were found to be 90.76 ± 1.56% and 208.24 ± 3.16 nm, respectively. The ibrutinib nanoliposomes were found to be stable both in simulated gastric and intestinal fluids at 37 °C for 6 h. At elevated conditions of temperature and pH, the prepared nanoliposomes were found to be unstable. Sonication for shorter periods resulted in decreased particle size, whereas longer periods can be helpful for ultrasound-assisted drug delivery. The closeness between the obtained results and predicted results indicates the reliability of the optimization technique for the preparation of ibrutinib nanoliposomes.

Funder

King Khalid University

Publisher

MDPI AG

Subject

Polymers and Plastics,General Chemistry

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