The role of the carrier in the formulation of pharmaceutical solid dispersions. Part I: crystalline and semi-crystalline carriers

ABSTRACT

Introduction: As a consequence of the target and drug candidate identification process, drugs with higher hydrophobicity and/or lipophilicity are being selected for further development, leading to solubility and dissolution rate limited oral bioavailability, and hence potential failure of the intended therapeutic goal. Solid dispersions were introduced as a formulation strategy in the early 1960s to tackle this issue and are still an area of intensive research activity.

Areas covered: There has been a shift in the type of carriers that were used in the formulation of solid dispersions as nowadays, amorphous carriers are most often used, whereas in early stages of solid dispersions development, crystalline and semi-crystalline carriers were most commonly applied. In this review, we will discuss several aspects related to the use of crystalline and semi-crystalline carriers such as their molecular and related physical structure, and their physical chemical properties related to formulation of poorly soluble drugs.

Expert opinion: The inherent crystallinity of this type of carrier hinders the formation of high-load solid solutions as mainly the amorphous domains of a carrier are able to accommodate drug molecules. Hence these carriers are not currently first choice excipients to formulate solid dispersions.

KEYWORDS:

• Citric acid
• crystalline carrier
• mannitol
• microstructure
• poorly soluble drugs
• polyethylene glycol
• semi-crystalline carrier
• solid dispersions
• urea

Article highlights

• Crystalline carriers can form solid dispersions that are eutectics, monotectics or interstitial solid solutions

• The API loading in crystalline and semi-crystalline carriers is generally lower than in amorphous polymeric carriers

• Polyethylene glycol is the most used non-amorphous polymer applied in solid dispersion preparation

• The stabilizing effect of drug-polymer interactions is less important when semi-crystalline or crystalline carriers are used as less interaction sites are available on the (semi)crystalline carrier

• Supersaturation maintenance of poorly soluble API is less pronounced in case (semi)crystalline carriers are used compared to amorphous polymers.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.