DissoCubes: A Novel Formulation to Enhance Solubility

About author
S.S Siddheshwar*, S.B. Somwanshi, R.T. Dolas, A.N. Merekar, R.K. Godge, S. R. Pattan
Department of Pharmaceutics, P.R.E.S.’s, Pravara Rural College of Pharmacy, Loni.
Department of Pharmaceutical Chemistry, P.R.E.S.’s, Pravara Rural College of Pharmacy, Loni.
E-mail: [email protected]

Abstract
Most of drugs are poorly soluble and have bioavailability problems. Therefore, there is an urgent need to find solutions for the formulation of these poorly soluble drugs. To achieve a broadly applicable technology, increasing interest has been focused on drug nanoparticles in the last few years. Going beyond micronization leads to a further increase in the dissolution velocity due to an even larger surfacearea. An additional effect can be achieved by a controlled structural change in drug nanoparticles, which means reducing the crystallinity and increasing the amorphous fraction eg Dissocubes. DissoCubes are crystalline nanoparticles of active substance obtained by a liquid state high energy process using a high pressure piston gap homogenizer to reduce the drug particle size in the presence of surface modifiers that associate at the freshly generated drug interface. A particle size reduction from approximately 50µm to about 0.5µm is achieved resulting in a very homogenous and stable formulation. The nanosuspensions could be formulated into various dosages forms. DissoCubes™ technology is a technology of choice for molecules with oral bioavailability issues and/or requiring rapid onset of absorption. However, there are two more interesting features of drug nanoparticles (i.e.,DissoCubes): (a) an increase in saturation solubility and (b) structural changes inside the particles.
Key words: DissoCubes, nanoparticles, nanosuspensions.
Introduction
Most of drugs are poorly soluble and have bioavailability problems. Therefore, there is an urgent need to find solutions for the formulation of these poorly soluble drugs. Preferably, such a new formulation principle should be applicable to almost any poorly soluble drug, independent of its chemical structure and spatial molecular dimensions. A simple approach to improve the bioavailability of orally administered drugs is micronization. However, especially for drugs with a low saturation solubility, the achieved increase in dissolution velocity might not lead to sufficiently high blood levels. Therefore, alternative formulation techniques to existing approaches need to be developed. To achieve a broadly applicable technology, increasing interest has been focused on drug nanoparticles in the last few years. Going beyond micronization leads to a further increase in the dissolution velocity due to an even larger surfacearea. An additional effect can be achieved by a controlled structural change in drug nanoparticles, which means reducing the crystallinity and increasing the amorphous fraction. Examples of drug nanoparticles with structural changes are the products NanoMorph^TM marketed by Knoll/BASF Pharma (company brochure) and the drug nanosuspensions marketed under the name DissoCubes . DissoCubes combine the advantages of using a size reduction technique (i.e., NonoCrystals) with the advantages of a precipitation technique(i.e., Hydrosols^TM, NanoMorph^TM) opening the opportunity to induce structural changes, which means increasing the amorphous fraction.