FIELD

The invention relates generally to devices and methods for dissolving sample substances such as drug molecules, in particular nanoparticles of drug molecules. The invention also relates to the use of the method and device for testing dissolution rates of the sample substance, and a kit to operationalize the method.

BACKGROUND

The dissolution rate of a drug is one of the primary physicochemical properties determined and modified during the drug discovery and development process. A way to increase the dissolution rate is to decrease the particle size. However, the study of dissolution rates of small particles, in particular nanoparticles, may be challenging. For example, it might be difficult to separate the dissolved fraction from non-dissolved particles for analysis.

The United States Pharmacopoeia (USP) I (basket) and II (paddle) methods have been modified for nanoparticle dissolution studies. Problems with the modified methods include migration of nanoparticles to interfaces e.g. by floating or adhesion, and by diffusional barriers (e.g. gelatin or dialysis membranes). The methods also require large amounts of solute and solvent with tedious sample preparation and separation steps before analysis. Separation steps such as filtration and centrifugation are often ineffective with nanoparticles and may significantly affect the dissolution processes. Additionally, adsorption to equipment and containers might become an issue. Therefore, these methods may be impractical when studying nanoparticle dissolution.

The USP IV flow-through apparatus has been found to be applicable for nanoparticle dissolution studies. However, the use of this apparatus has challenges related to filtering. Too large filter pore size leads to particles escaping and consequently to overestimating the dissolution rate, while too narrow pore size leads to clogging and even breaking of the filter.

Drug nanoparticles can be analyzed as tablets and as admixed with gel matrices. However, the tableting process may alter the physical form of the drug. It has also been found that particles may detach from the tablet surface during dissolution, thus invalidating the dissolution tests. Analysis of dissolution tests of nanoparticles admixed with gel matrices, in turn, may be complicated by the diffusion of the drug in the matrix.

Accordingly, there is a need for new methods and devices for determining dissolution rates of sample substances that are suitable also for nanoparticles.

SUMMARY

The following presents a simplified summary in order to provide a basic understanding of some aspects of various embodiments of the invention. The summary is not an extensive overview of the invention. It is neither intended to identify key nor critical elements of the invention, nor to delineate the scope of the invention. The following summary merely presents some concepts of the invention in a simplified form as a prelude to a more detailed description of exemplifying embodiments of the invention.

In accordance with the invention, there is provided a new device for dissolving a sample substance, the device comprisinga shell matrix comprising a first lyophilic material, anda cage comprising at least one hole.

According to the invention, the shell matrix is adapted to cover the sample substance to form a shell matrix-sample substance system. The shell matrix-sample system is adapted to be inserted into the cage.

In accordance with the invention, there is provided also a new method for dissolving a sample substance, the method comprisingproviding a sample substance,covering the sample substance with a shell matrix comprising a first lyophilic material to form a shell matrix-sample substance system,inserting the shell matrix-sample substance system into a cage comprising at least one hole, andexposing the cage comprising shell matrix-sample substance system to a medium capable of dissolving the sample substance.

In accordance with the invention, there is provided also a new method for determining one of more dissolution properties of a sample substance, the method comprisingdissolving the sample substance into a dissolution medium by a method according to any of claims6-12, anddetermining at least one dissolution property of the sample substance in the dissolution medium.

In accordance with the invention there is also provided a method for controlling a process for producing a substance, the method comprising,

(i) producing a substance,

(ii) providing a sample substance by collecting a sample of the substance,

(iii) determining one or more dissolution properties of the sample substance according to claim13,

(iv) comparing the one of more dissolution properties of the sample substance to one or more predetermined dissolution properties, and

(v) optionally modifying the producing based on the comparing.

In accordance with the invention, there is also provided a kit for use in a method according to any of claims6-14, comprising a device according any of claims1-5, and a lyophilic material for a sample substance.

A number of exemplifying and non-limiting embodiments of the invention are described in accompanied dependent claims.

Various exemplifying and non-limiting embodiments of the invention both as to constructions and to methods of operation, together with additional objects and advantages thereof, are best understood from the following description of specific exemplifying embodiments when read in connection with the accompanying drawings.

The verbs “to comprise” and “to include” are used in this document as open limitations that neither exclude nor require the existence of also unrecited features. The features recited in depending claims are mutually freely combinable unless otherwise explicitly stated. Furthermore, it is to be understood that the use of “a” or “an”, i.e. a singular form, throughout this document does not exclude a plurality.

