Celecoxib-hydroxypropyl-ß-cyclodextrin inclusion complex in a chitosan/PEO-PPO-PEO block copolymer matrix: Structural effect and drug release.

HYPOTHESIS: Triblock copolymers of poly(ethylene oxide) and poly(propylene oxide)-based matrices, such as Poloxamer 407 (P407) or Pluronic® F127, are extensively utilized in drug delivery and permeation systems due to their FDA approval and listing in the US and European Pharmacopoeias. The study hypothesizes that incorporating 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) and the celecoxib-HP-ß-CD inclusion complex into a 16 wt% P407 and chitosan blend in an aqueous acetic acid solution will affect the system's rheological and structural properties. EXPERIMENTS: Rheological, small-angle X-ray scattering (SAXS), and dynamic light scattering (DLS) experiments were conducted to assess the impact of acetic acid and chitosan on the 16 wt% P407 and chitosan blend. Additionally, in vitro drug release studies were performed to monitor the drug release profile over time. FINDINGS: The addition of HP-ß-CD was found to inhibit gel formation in the 16 wt% P407 and chitosan blend. However, the presence of the celecoxib-HP-ß-CD inclusion complex showed no significant structural effects compared to P407 blended with chitosan alone. Rheological and SAXS analyses demonstrated that acetic acid led to the formation of a lamellar phase due to the lower pH, facilitating injectability. The presence of chitosan in acetic acid resulted in the detection of a hexagonal phase, affecting the release of celecoxib.

Boric Acid, a Lewis Acid With Unique and Unusual Properties: Formulation Implications.

This review provides insight into the use of boric acid as a pharmaceutical, a buffer, and an adjuvant/excipient in pharmaceutical formulations. Boric acid is a Lewis acid with a pKa of 8.92-9.24 that is sensitive to temperature, ionic strength, and concentration. The pKa varies with concentration because of polymerization above 0.02 M. Boric acid reacts reversibly with alcohols, especially 1,2-diols including carbohydrates, with carboxylic acids, thiols, and amines. These esters/adducts, are also Lewis acids with lower pKa values. Boric acid can stabilize some materials while catalyzing the degradation of others. Boric acid is used in various dermal and women's hygiene products because of its mild antibacterial and antifungal activity. In ophthalmic products, it is used as a buffer and in combination with other preservatives to broaden the prservative spectrum. Boric acid has been used reluctantly in parenteral products but appears to be quite safe at low doses. However, at high exposure, toxicity, including death, has been reported in humans, especially in children. Animal toxicities have also been noted, including reductions in male sperm counts. Boric acid is well absorbed on oral dosing. Its biological half-life is about 21 h in humans and has an affinity for some tissues, especially bone.