Preparation study and bioavability evaluation of tablets containing fenofibrate nanoparticles
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The Fenofibrate tablet used was a high-tech dosage form, containing fenofibrate nanoparticles. Its advantage was a high bioavailability that was not affected by meal. This study aimed to prepare tablets containing fenofibrate nanoparticles with the same dose and bioavailability as the reference drug (Lipanthyl 145). The study developed a formula of nano fenofibrate suspension including fenofibrate 1,5g, HPC 0,05g, HPMC E6 0,025g, water 5g by wet ball milling. The suspension had a size less than 500nm and the ratio of fenofibrate was nano-sized to 70% after centrifuging at 100 rcf. Fenofibrate granules were made by fluid-bed granulation from milling suspension and fabricated tablet containing 145 mg of fenofibrate. The tablet had dissolution similar to the reference drug. The oral bioavailability of the studied tablets was compared to the reference drug in drugs according to the model of double crossover principle, two doses, two drugs, two periods, two sequences. The results of AUClast (µg*h/mL), Cmax (µg/mL), Tmax (h) of the studied tablet and reference drug were (45.473; 5.899; 2.625) and (46.019; 5.814; 2.583) respectively. This result showed that preparing nano fenofibrate-containing dosage form equivalent to the reference drug was feasible.
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Tóm tắt
Fenofibrat là thuốc có dạng bào chế công nghệ cao, chứa các tiểu phân nano fenofibrat. Ưu điểm của thuốc là có sinh khả dụng cao và không bị ảnh hưởng bởi thức ăn. Nghiên cứu thực hiện nhằm mục tiêu bào chế và đánh giá được tiểu phân nano fenofibrat bằng phương pháp nghiền bi, bào chế viên nén và đánh giá sinh khả dụng của viên nén chứa tiểu phân nano fenofibrat. Nghiên cứu đã xây dựng được công thức hỗn dịch nghiền bi bao gồm fenofibrat 1,5 g, HPC 0,05 g, HPMC E6 0,025 g, nước 5 g. Dịch sau nghiền có kích thước <500 nm, tỉ lệ dược chất được nano hóa 70%. Nghiên cứu đã rắn hóa dịch nghiền và xây dựng được công thức viên nén chứa 145 mg fenofibrat, viên nén có độ hòa tan tương đương thuốc gốc. So sánh sinh khả dụng của viên nén nghiên cứu được và thuốc đối chiếu Lipanthyl 145 mg được thực hiện trên chó theo nguyên tắc chéo đôi, 2 liều 2 thuốc 2 giai đoạn 2 trình tự. Kết quả AUClast (µg*h/mL) Cmax (µg/mL), Tmax (h) của thuốc thử và thuốc chứng lần lượt là (45,473; 5,899; 2,625) và (46,019; 5,814; 2,583). Kết quả này cho thấy việc bào chế thuốc fenofibrat dạng nano tương đương với thuốc gốc có tính khả thi.
Abstract
The Fenofibrate tablet used was a high-tech dosage form, containing fenofibrate nanoparticles. Its advantage was a high bioavailability that was not affected by meal. This study aimed to prepare tablets containing fenofibrate nanoparticles with the same dose and bioavailability as the reference drug (Lipanthyl 145). The study developed a formula of nano fenofibrate suspension including fenofibrate 1,5g, HPC 0,05g, HPMC E6 0,025g, water 5g by wet ball milling. The suspension had a size less than 500nm and the ratio of fenofibrate was nano-sized to 70% after centrifuging at 100 rcf. Fenofibrate granules were made by fluid-bed granulation from milling suspension and fabricated tablet containing 145 mg of fenofibrate. The tablet had dissolution similar to the reference drug. The oral bioavailability of the studied tablets was compared to the reference drug in drugs according to the model of double crossover principle, two doses, two drugs, two periods, two sequences. The results of AUClast (µg*h/mL), Cmax (µg/mL), Tmax (h) of the studied tablet and reference drug were (45.473; 5.899; 2.625) and (46.019; 5.814; 2.583) respectively. This result showed that preparing nano fenofibrate-containing dosage form equivalent to the reference drug was feasible.
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