Bridging the Gap Between API and Drug Product

DS-DP co-processing is used extensively at CfPC to align both API and drug product development and to overcome potential hurdles in drug development. In solid-dosage processes, the API is generally blended with excipients via wet or dry granulation. Co-processing is a relatively new area of particle engineering in which commonly used excipients can be combined with the API in a more deliberate and controlled manner to design a pharmaceutical composite material.1Saffari, Morteza et al, “A Novel Formulation for Solubility and Content Uniformity Enhancement of Poorly Water-Soluble Drugs Using Highly-Porous Mannitol,” Eur. J. Pharm. Sci. 83 (2016): 52–61. 2Yazdanpanah, Nima et al., “Continuous Heterogeneous Crystallization on Excipient Surfaces,” Cryst. Growth Des. 17, No. 6 (2017): 3321–3330. This approach combines two or more materials in a specific way to produce a composite material with improved physical or chemical properties. A process can be designed to resolve some of the common issues related to solid dosage production, such as material fl ow, stability, compactibility, release profile, bioavailability, food effect, content uniformity, taste, and even containment issues related to potent or toxic compounds.

At CfPC, crystallization efforts and form selection of APIs are closely integrated with the requirements of overall product development. As an example, for amorphous compounds, the end-point API is an intermediate co-processed in a dispersion with suitable formulation excipients to provide enhanced physical and chemical properties, such as stability, flow, and bioavailability, as evidenced by increased solubility and dissolution. 3Qian, F. et al., “Drug–Polymer Solubility and Miscibility: Stability Consideration and Practical Challenges in Amorphous Solid Dispersion Development,” J. Pharm. Sci. 99, No. 7 (2010): 2941–2947.

Milling of Bulk API

Dry Milling: co-mill jet mill

Wet Milling: beads milling KA mill sonication

Controlled Crystallization Process

Growth dominated crystallization

Nucleation dominated crystallization

Nucleation + Growth

Spherical crystallization

Wet milling applications

DS-DP Co-Processing

Spray dried dispersions

Microsphere formation

Excipient modified crystallization

Crystallization inside porous excipient(s)