Technology

Rilento is focusing our design and development expertise on the acute post-surgical dental pain space. Demonstrating the efficacy of these drug delivery systems with a variety of drugs can be extended from the oral surgery model to other forms of tissue injury and post-surgical pain as a preventive strategy to minimize the need to administer opioid drug combinations.

The delivery systems are designed to administer anesthetic alone or anesthetic with analgesic drugs that have anti-inflammatory properties to suppress the acute inflammatory process by inhibiting both COX1 and COX2 over the first 24-48 hours when prostanoids are driving acute pain, edema and the process of sensitization leading to hyperalgesia. When combined with a long acting local anesthetic, the initial nociceptive pain is suppressed and also minimizes sensitization. The timed release of anesthetics over the 72-hour postoperative course is additive with these actions to reduce any residual pain, potentially resulting in minimal pain and loss of function over the postoperative course.

Cyclooxygenase-1 (Prostaglandin Synthase-1) in complex with a COX-1 selective inhibitor ⁽¹⁾

Cyclooxygenase-2 (Prostaglandin Synthase-2) in complex with a COX-2 selective inhibitor ⁽²⁾

(1) PDB: 1CQE; Picot D, Loll PJ, Garavito RM (January 1994). "The X-ray crystal structure of the membrane protein prostaglandin H2 synthase-1". Nature. 367 (6460): 243–9. doi:10.1038/367243a0. PMID 8121489.

(2) PDB: 6COX; Kurumbail RG, Stevens AM, Gierse JK, McDonald JJ, Stegeman RA, Pak JY, Gildehaus D, Miyashiro JM, Penning TD, Seibert K, Isakson PC, Stallings WC (1996). "Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents". Nature. 384 (6610): 644–8. doi:10.1038/384644a0. PMID 8967954.

Rilento employs a micro-compounding approach developed with an eye to manufacturability. Drug and additive release profile responses are modeled along with end-use responses to achieve a navigable design space as a function of all formulation factors for co-optimization of the response sets. For example, in our oral surgery work we are co-optimizing the release responses and rheological responses that impact manufacturability and end-use tactile characteristics.

Formulation vehicles are being designed to co-disperse binder systems together with multi-modal particle size distributions of active-ingredients (anesthetics, analgesics, additives) into bioresorbable polymer-encapsulated particles within hydrophobic/hydrophilic and pH modulated phases. Although the state of dispersion can be regarded as an important factor that impacts the release profile, the key to release performance is in achieving reproducibility and consistency for any given state of dispersion (i.e., for a state of dispersion that simultaneously satisfies manufacturing constraints and end-use performance targets).