Undoubtedly, one of the major challenges for Active Pharmaceutical Ingredient (API) in getting success through formulation development is the API solubility. The ability of a solute to get dissolved in a solvent in a homogeneous manner is termed as solubility. As a result, in pharmaceutical terms- it is necessary to realize the desired concentration of any drug in a systematic circulation for an anticipated pharmaceutical response.
Still, there are more than 40% of all New Chemical Entities (NCEs) that have less than ideal solubility. So, in order to overcome these challenges, different pharmaceutical manufacturers have introduced a wide range of excellent and steadily improving techniques that are able to provide acceptable solubility. The first thing to be done in order to improve the formulation development is to understand the importance of API characterization of the chemicals.
Understanding the Importance of API Characterization
The common approach of the formulators is to start with a detailed characterization of the physical as well as chemical characteristics of the API. This is the fundamental step that should not be ignored, which could sometimes result in some of the disastrous consequences for the project economics as well as the timeline. Along with the detailed study of the of the API crystal structure, it is good to recognize the changes while providing improved solubility.
It could be observed that the API characteristics usually changes with the increased batch size of the product, but there is a definite baseline that will help in comparing these changes by highlighting the differences and making required modifications. Without having a basic knowledge, the challenges that arise later on are difficult to evaluate as well as respond for resulting in the unplanned changes to the costs as well as timelines.
There are some of the definite methods for enhancing the solubility of some of the poorly soluble chemical APIs. Let us have a brief overview of those methods:
In the early development lifecycle of the APIs, the physical modifications of the APIs are possible. An amorphous API or a salt form may be selected that has better solubility as it is easy to make modifications during the synthesis process. The Micronization could also increase the surface area in order to help the dissolution of the API.
The main components that fall under the physical manipulation category include nanosuspension, co-crystallization and drug dispersion in carriers, modification of the crystal structure like the polymorphs, solid dispersion, cryogenic techniques and many more fall under this category. Another technique is the hot melt extrusion that can be used for the waxy materials as well as to create a controlled-release formulations.
In this process, the changing pH can improve the solubility of the API chemicals. It can be used for the buffer, complexation, derivitization as well as salt formation processes. In order to increase the solubility of the chemicals, the additional surfactants or the cyclodextrins can be used for resulting more chemical manipulation.
Lipid Based Formulations:
The lipid based formulations could improve the solubility as well as the dissolution rate of the API. This could lead to the consideration of the liquid-filled capsule approach in order to increase the solubility. Various lipophilic excipients like the Gelucires could help in improving the solubility as well as the bioavailability of the API. Using a self-emulsifying drug delivery system (SEDDS) formulation helps in improving the solubility as well as possibly permeability. The lipid base formulation approach may work better with the APIs that are lipophilic and that can easily go into solutions with the excipients like the olive oil.
The API solubility generally seems to be one of the most difficult obstacles to get success in API formulation development. Generally, the experienced formulators have the knowledge to come up with the unique engineering solutions, particularly for those having trouble to deal with. There are a number of methods or options for the formulation development, but it’s quite difficult to experience the solubility or bioavailability in a timely as well as economic manner.
Written by Dangiel Clark