Buccal delivery of drugs provides an attractive alternative to the oral route of drug administration, particularly in overcoming deficiencies associated with the latter mode of administration. Problems such as high first-pass metabolism and drug degradation in the harsh gastrointestinal environment can be circumvented by administering the drug via the buccal route (1-3). Moreover, buccal drug absorption can be promptly terminated in case of toxicity by removing the dosage form from the buccal cavity. It is also possible to administer drugs to patients who cannot be dosed orally to prevent accidental swallowing. Therefore adhesive mucosal dosage forms were suggested for oral delivery, which included adhesive tablets (4-6), adhesive gels (7, 8) and adhesive patches (9, 10). Buccoadhesive tablets of carvedilol were prepared using HPMC K4M, HPMC K15M and Carbopol 934 as mucoadhesive polymers. Fifteen formulations were developed with varying concentrations of polymers. Formulations of the BC or BD series were composed of HPMC K4M or HPMC K15M in ratios of 1:1 to 1:5 whereas in the BE series Carbopol 934 was used (1:0.25 to 1:1.50). The formulations were tested for in vitro drug release, in vitro bioadhesion, moisture absorption and in vitro drug permeation through porcine buccal mucosa. Formulation BC3 showed maximum release of the drug (88.7 ± 0.4%) with the Higuchi model release profile and permeated 21.5 ± 2.9% of the drug (flux 8.35 ± 0.291 µg h -1 cm -2 ) permeation coefficient 1.34 ± 0.05 cm h -1 ) through porcine buccal membrane. BC3 formulation showed 1.62 ± 0.15 N of peak detachment force and 0.24 ± 0.11 mJ of work of adhesion. FTIR results showed no evidence of interaction between the drug and polymers. XRD study revealed that the drug is in crystalline form in the polymer matrix. The results indicate that suitable bioadhesive buccal tablets with desired permeability could be prepared.

BackgroundBleomycin sulfate is a metal‐complexing glycopeptide that is commonly used as an experimental model for pulmonary fibrosis. Pulmonary fibrosis induced by Bleomycin sulfate is mediated via DNA damage and cytotoxic actions on the alveolar epithelial cells. Among various factors, the in vitro actions of Bleomycin sulfate depend considerably on its chemical stability and the solvent used to dissolve the drug. In this study, we evaluated the effects of various solvents [water, dimethyl sulfoxide (DMSO), saline and Dulbecco's Modified Eagle Medium (DMEM)] on the in vitro cytotoxic activity and stability of Bleomycin.MethodsThe cytotoxic effect of Bleomycin sulfate was evaluated on alveolar epithelial cells (A549) using various concentration (10, 15 and 20 mcg/mL) of the drug dissolved in different solvents. A549 cells were seeded at a concentration of 5 × 103 cells per well in a 96 well‐plate and incubated for 24 hours. These cells were then exposed to various concentrations of Bleomycin sulfate in the different solvents for the next 24 hours. The cell viability was determined using the MTT (3‐(4, 5‐dimethylthiazolyl‐2)‐2, 5‐diphenyltetrazolium bromide) reduction assay.ResultsSignificant cytotoxic response was observed with all the doses of Bleomycin sulfate (10, 15 and 20 mcg/mL) when it was dissolved in either water or DMSO. However, this was not the case with DMEM or saline since lower concentration of Bleomycin sulfate (10 mcg/mL) failed to induce cell death. We noticed that treatment of A549 cells with any of the solvents by themselves (vehicle control) did not induce cell death. With regards to DMSO, we used a final concentration of 0.025% v/v in the cell culture media.ConclusionWe conclude that water or DMSO (at a final concentration of 0.025% v/v) may serve as suitable solvents to dissolve Bleomycin sulfate for carrying out in vitro cell culture assays. Also, it appears that higher concentrations of Bleomycin sulfate are required to show cytotoxic activity when DMEM or saline is used as a solvent. Further studies are warranted using high performance liquid chromatography (HPLC) to explore drug stability in the various solvents used.Support or Funding InformationSeed Funding from California Health Sciences UniversityThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.