Formulation and evaluation of controlled-release transdermal patches of theophylline-salbutamol sulfate.
Transdermal formulations containing theophylline and salbutamol sulfate (SS) were formulated using hydroxypropylmethylcellulose. Theophylline was loaded by adsorption with the aid of the coadsorbate sodium chloride. The formulations were subjected to in vitro release studies, and the dose of salbutamol and theophylline was optimized to yield the desired flux. The films were uniform and 93 +/- 5.4 microm thick. The in vitro fluxes of theophylline and salbutamol sulfate from the formulation were 1.22 +/- 0.4 mg/h/cm2 and 13.36 +/- 1.02 microg/h/cm2, respectively. The formulation was subjected to pharmacodynamic studies in guinea pigs. The preconvulsive time (PCT) of guinea pigs increased significantly after 4 h, and the same was observed even after 24 h Pharmacokinetic studies were carried out in healthy human volunteers. Theophylline was analyzed in saliva, and salbutamol was analyzed in the blood plasma. The Tmax of the drugs was 3 h, and appreciable concentrations of the drugs above their MEC could be analyzed even after 12 h. The elimination half-life of the drugs was significantly prolonged compared to that for tablets. There were no signs of erythema or edema in the volunteers during observation for a period of 7 days.
Murthy
S N
SN
M. S. Ramaiah College of Pharmacy, Bangalore, India.
Rani
S
S
Hiremath
R
R
D000042:Absorption; D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D065347:Hypromellose Derivatives; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D012463:Saliva / Q000737:chemistry; D013806:Theophylline / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics
D001993:Bronchodilator Agents; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D013806:Theophylline; D000420:Albuterol