Arginine Complexes with Simvastatin: Apparent Solubility, In Vitro Dissolution and Solid State Characterization

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery
• Physical Chemistry

Background:

• Statins, classified as Biopharmaceutics Classification System (BCS) Class II drugs, suffer from poor aqueous solubility and bioavailability.
• This limitation poses significant challenges for formulation scientists.
• Simvastatin (SMV), a widely prescribed statin, exemplifies these formulation difficulties.

Purpose of the Study:

• To develop a de novo approach for enhancing the aqueous solubility of simvastatin.
• To create a complex between simvastatin and the cosolute arginine (SMV-ARG).
• To evaluate the impact of this complexation on solubility and dissolution characteristics.

Main Methods:

• Complex formation between simvastatin (SMV) and arginine (ARG).
• Characterization of the SMV-ARG complex for apparent solubility and in vitro dissolution.
• Solid-state characterization using FTIR, Elemental Analysis, XRD, DSC, TGA, and SEM.

Main Results:

• The SMV-ARG complex demonstrated a remarkable 12,000-fold increase in apparent solubility.
• Significant improvements in in vitro dissolution were observed in both acidic and alkaline media.
• Solid-state analysis indicated a conversion from a crystalline to a non-coherent and partially amorphous pattern, correlating with enhanced solubility.

Conclusions:

• Arginine effectively forms complexes with small molecules like simvastatin, substantially increasing their aqueous solubility.
• This complexation strategy presents a valuable approach for drug formulation and development, particularly for poorly soluble compounds.
• The findings support the utility of arginine as a cosolute for enhancing the pharmaceutical properties of BCS Class II drugs.