Fast-disintegrating sublingual tablets: effect of epinephrine load on tablet characteristics.
The aim of this study was to evaluate the effect of increasing epinephrine load on the characteristics of fast-disintegrating sublingual tablets for the potential emergency treatment of anaphylaxis. Four tablet formulations, A, B, C, and D, containing 0%, 6%, 12%, and 24% of epinephrine bitartrate, respectively, and microcrystalline cellulose:low-substituted hydroxypropyl cellulose (9:1), were prepared by direct compression, at a range of compression forces. Tablet weight variation, content uniformity, hardness, disintegration time, wetting time, and friability were measured for each formulation at each compression force. All 4 tablet formulations at each compression force were within the United States Pharmacopeia (USP) limits for weight variation and content uniformity. A linear increase in compression force resulted in an exponential increase in hardness for all formulations, a linear increase in disintegration and wetting times of A, and an exponential increase in disintegration and wetting times of B, C, and D. At a mean +/- SD hardness of > or = 2.3 +/- 0.2 kg, all tablet formulations passed the USP friability test. At a mean +/- SD hardness of < or = 3.1 +/- 0.2 kg, all tablet formulations resulted in disintegration and wetting times of <10 seconds and <30 seconds, respectively. Tablets with drug loads from 0% to 24% epinephrine can be formulated with hardness, disintegration times, and wetting times suitable for sublingual administration.
Rawas-Qalaji
Mutasem M
MM
Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada.
Simons
F Estelle R
FE
Simons
Keith J
KJ
D000284:Administration, Oral; D000707:Anaphylaxis / Q000188:drug therapy; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D020099:Coated Materials, Biocompatible / Q000032:analysis / Q000737:chemistry*; D004058:Diffusion; D004353:Drug Evaluation, Preclinical; D004837:Epinephrine / Q000008:administration & dosage* / Q000032:analysis / Q000737:chemistry*; D006244:Hardness; D006801:Humans; D007700:Kinetics; D008422:Materials Testing; D010316:Particle Size; D012463:Saliva / Q000737:chemistry*; D012995:Solubility; D013499:Surface Properties; D013607:Tablets / Q000032:analysis / Q000737:chemistry*; D013997:Time Factors; D014059:Tongue / Q000737:chemistry*
D020099:Coated Materials, Biocompatible; D013607:Tablets; D004837:Epinephrine