Cyclosporine A solid self-microemulsion particles and preparation method thereof

Abstract

The invention relates to the field of medical technology, in particular to a cyclosporine A solid self-microemulsion particle and a preparation method of the cyclosporine A solid self-microemulsion particle. The preparation method is characterized in that spherocrystal granulation technique is utilized, cyclosporine A self-microemulsion is added to a uniform suspension solution of a polymer material formed by the high polymer material, a dispersion carrier and a pore-forming agent by dissolution in a solvent, the suspension solution is added to a poor solvent containing a surfactant, and cyclosporine A solid self-microemulsion particle is prepared in liquid phase in one step. The cyclosporine A solid self-microemulsion particle comprises the following ingredients by weight: 0.25 to 1.5% of cyclosporine A, 4.0% of polyoxyethylene hydrogenated castor oil, 2.0% of caprylic / decanoic acid glycerol ester, 2.0% of propylene glycol, 1.0% of ethanol, 4.0% of dichloromethane, 0.5-1.1g of ethyl cellulose (or Eudragit RS100, RS100), 0.05 % of PEG4000 (polyethylene glycol 4000) and 0.5% of colloidal silicon dioxide.

Description

1. Technical field [0001] The invention belongs to the technical field of medicine, and relates to a preparation method of a pharmaceutical preparation, specifically a cyclosporin A solid self-microemulsion particle and a preparation method thereof. Specifically, it is a kind of cyclosporin A solid self-microemulsion particle prepared in one step in the liquid phase. 2. Background technology [0002] Cyclosporine A is a potent immunosuppressant, and has been widely used in patients with liver, kidney, lung, bone marrow, pancreas and other organ transplants to resist rejection and autoimmune diseases such as psoriasis, rheumatoid arthritis, etc. disease treatment. Cyclosporin A has a large molecular weight (1202.6), strong lipophilicity (lgP=2.92) and low water solubility (37°C, 1.73 μg / ml), and is highly dependent on bile absorption and has extensive gastrointestinal metabolism. Therefore, oral absorption is poor, bioavailability is low, and individual differences are larg...

AI Technical Summary

Problems solved by technology

Cyclosporin A has a large molecular weight (1202.6), strong lipophilicity (lgP=2.92) and low water solubility (37°C, 1.73 μg / ml), and is highly dependent on bile absorption and has extensive gastrointestinal metabolism. Therefore, oral absorption is poor, bioavailability is low, and individual differences are large, which limits its wide application in clinical practice.

The dosage forms currently on the market are soft capsules, oral liquids and injections. The drug will self-emulsify and form a microemulsion when it encounters water in the body, which improves the problems of low bioavailability of the drug and large individual differences among patients.

Neoral, a commercially available preparation, can automatically emulsify into a microemulsion of about 30nm after being taken orally in contact with gastrointestinal fluids, which improves the shortcomings of low oral bioavailability and large pharmacokinetic variability of CyA, but the self-microemulsion contains a large amount of The solubilizer CremophorEL can cause a series of biological and physiological side effects, such as nephrotoxicity, allergic reaction, hyperlipidemia, red blood cell aggregation, etc., and it is easy to appear the problem of high drug concentration in the short term after taking the drug and low drug concentration in the later stage according to the blood drug concentration monitoring

[0003] Due to the high viscosity of the oil phase and surfactant contained in the self-microemulsion, the spray drying yield is low; the freeze-drying method has certain requirements on the equipment, the cost is high, and the production is complicated; the ordinary carrier adsorption method generally needs to add a large amount of carrier excipients. agent, the prepared solid powder has low drug loading and high viscosity, which is difficult to handle, etc.

The research group intends to explore a new way to prepare solid self-microemulsions by spherulite granulation technology. At present, there are no reports on the preparation of solid self-microemulsions by spherulite granulation technology in the literature and patents.

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