Browse Prior Art Database

Pharmaceutical Formulations of 2-Amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol

IP.com Disclosure Number: IPCOM000242164D
Publication Date: 2015-Jun-22
Document File: 4 page(s) / 570K

Publishing Venue

The IP.com Prior Art Database

Abstract

The poor physicochemical properties of Lurasidone, in particular, the poor water solubility and strong protein binding pose serious problems for manufacturing solid oral pharmaceutical composition. Because of poor water solubility, it is difficult to prepare a pharmaceutical preparation having equivalent dissolution profile, and even more challenging to have such equivalent in vitro (dissolution) profile over a wide range of medicament content. Described herein are suitable solid oral formulations of lurasidone which have acceptable dissolution profile.

This text was extracted from a PDF file.
This is the abbreviated version, containing approximately 52% of the total text.

Page 01 of 4

"Pharmaceutical Formulations of 2-Amino-2-[2-(4-octylphenyl)ethyl] propane-1, 3-diol"

The chemical compound, (3aR,4S,7R,7aS)-2-{(1R,2R)-2-[4-(1,2-benzisothiazol-3-yl)piperazin1yl- methyl]cyclohexylmethyl}hexahydro-4,7-methano-2H-isoindole-1,3-dione hydrochloride, generically known as 'Lurasidone' has the following structure:

Lurasidone approved by USFDA for the treatment of schizophrenia and depressive episodes generation antipsychotic drug characterized by a multi-receptor profile. Besides having high affinity for 5-HT2Aand D2receptors, it is also characterized by potent 5-HT7 receptor antagonism.

The poor physicochemical properties of Lurasidone, in particular, the poor water solubility and strong protein binding pose serious problems for manufacturing solid oral pharmaceutical composition. It has an aqueous solubility of 0.224 mg/ml in water with maximum solubility of 0.349 mg/ml in pH 3.5 buffer. Because of poor water solubility, it is difficult to prepare a pharmaceutical preparation having equivalent dissolution profile, and even more challenging to have such equivalent in vitro (dissolution) profile over a wide range of medicament content.

Various solid oral pharmaceutical compositions of Lurasidone hydrochloride containing excipients as summarised in Table - 1 were prepared. The composition may be in the form of a powder, granule or pellets or a unit dosage form, for example such as a tablet or capsule. The pharmaceutical compositions were produced by standard processes, for instance by dry granulation, wet granulation, direct compression. Conventional blending, granulating, sugar-coating, dissolving or lyophilizing processes may be employed in the preparation of pharmaceutical dosage form and the preparation may be formulated by a conventional method into tablet, capsule, granule or fine granule by using water-soluble excipient as well as water-insoluble excipient, binder, disintegrant, lubricant, etc.

Further, the dosage formulation comprises the active agent and excipients in the form of particles having a particle size distribution that allows for the ease of processing the material, for example into capsules or tablets, without segregation of the excipients. The desired particle range of active agent and excipients and other components may be obtained by processes known in the art, including granulating, screening, milling, and the like. Preferably the lurasidone used for making the solid oral prepration has particles size of D0.9 less than 10 ยต. The prepared dosage form may contain lurasidone hydrochloride in the range of 20 to 120 mg per tablet.

A typical process for formulating the solid oral preparation i...