| Our Bioadhesive Delivery System |
Each of Columbia’s marketed products and product candidates utilizes our novel bioadhesive drug delivery system (BDS), an innovative technology that differentiates. Columbia from its competitors and provides a platform for numerous additional applications in the future. The key ingredient in the BDS is polycarbophil, a non-immunogenic, hypo-allergenic, bioadhesive polymer. Polycarbophil bonds to the cells of the body’s mucosal surfaces upon administration. In our vaginally-administered products, it bonds to the vaginal epithelial cells. In our buccal products, it adheres to the cells of the oral mucosa. Once in place, the BDS releases the active drug in a controlled and sustained manner until it is discharged upon normal cell turnover. This occurs every three to five days for the vaginal epithelium and up to every 24 hours for the oral mucosa.
Bioadhesive Gels and Progressive Hydration Tablets
The Company’s bioadhesive vaginal gels are comprised of an active drug entrapped in the BDS. They are self- administered using a patient-friendly, pre-filled applicator. The progressive hydration tablets, including the buccal system and an investigational vaginal tablet, contain the active drug, polycarbophil and a water-soluble carbomer. As the tablet absorbs water, the active drug is gradually released and absorbed across the mucosal surface to which the product is bonded. Meanwhile, the active ingredient is protected from the surrounding environment, preventing it from being metabolized or degraded by moisture, enzymes or pH effects.
The Chemistry of BDS Bioadhesion
Polycarbophil is lightly cross-linked with divinyl glycol. It is a weak polyacrylic acid (pKa = 4.2) containing multiple carboxyl radicals (COO-), which are the source of its negative charges. These acid radicals permit hydrogen bonding with the cell surface. Hydrogen bonds are weak, but in the case of polycarbophil they are numerous and therefore tenacious. |
Polycarbophil mimics negatively charged mucin, the glycoprotein component of mucus responsible for its attachment to underlying epithelial surfaces.
The Compelling Argument for Bioadhesive Vaginal Delivery
Bioadhesive vaginal delivery, whether in our bioadhesive gel or progressive hydration tablet, facilitates targeted delivery of active compounds to the uterus, right where they are needed. Vaginal administration of progesterone avoids the local site pain, irritation and potential infection of daily compounded progesterone intramuscular injections. The BDS’ bioadhesive properties ensure CRINONE® 8% , PROCHIEVE® 8% and PROCHIEVE 4% (progesterone gels) achieve and sustain high levels of progesterone in the uterus, where it is needed, while maintaining low systemic levels. The BDS and pre-filled applicators make these FDA-approved products easy to use and patient-friendly, without the mess of pharmacy-compounded suppositories.
|
|
Columbia’s BDS technology is currently being used to develop bioadhesive, vaginally-administered lidocaine, terbutaline, testosterone, and carbamide peroxide products for various women’s healthcare indications.
The Benefits of Buccal Delivery
Our unique buccal delivery system facilitates absorption of the active drug, for example, testosterone, through the gum and cheek and directly into the superior vena cava, bypassing the gastrointestinal system and liver. Buccal delivery of testosterone avoids the skin irritation and transference issues inherent with transdermal testosterone delivery via patches and gels, and the local site pain, irritation and potential infection of injectible testosterone. Columbia has applied the buccal system to desmopressin, a short-chain peptide, for nocturnal enuresis in children. We seek to partner this developmental-stage project with a company in whose strategic focus it fits.
Broad Utility for Future Product Development
While Columbia’s targeted BDS technology has particular utility for molecules with low oral bioavailability, when extended duration of effectiveness is desirable, or where systemic levels of the active ingredient must be curtailed, the BDS can deliver many types of compounds to address a host of medical conditions. In addition to proprietary product development, this facility invites collaboration with other companies to develop BDS products with their compounds for indications other than women’s healthcare. |
|
