Transdermal drug delivery system of haloperidol to overcome self-induced extrapyramidal syndrome.
Haloperidol (HAL), an antipsychotic, is associated with side effects of drug-induced extrapyramidal syndrome (EPS) in conventional monotherapy. Controlled released transdermal dosage form (TDDS) of the drug was designed for maintenance therapy. Matrix-diffusion type transdermal film of HAL was designed with Eudragit NE 30D copolymer without permeation enhancer in different combinations. For the feasibility studies, all standard evaluations were performed, and their results pointed toward the suitability of TDDS. The drug release and permeation studies in Franz diffusion cell in 20% PEG-normal saline followed the Higuchi equation with optimum correlation coefficient. The neuroleptic efficacy was confirmed by maximum graded response in a rotarod apparatus. The neuroleptic-induced catatonia (EPS) in albino rats was minimum with a score of zero over a 72-hr study. The pharmacokinetic parameters in rabbit model showed a very significant prolongation of action up to 72 hr with steady-state plasma concentration (cp(ss)) of 11.58 ng/mL. Thus, the HAL-loaded TDDS improved the therapeutic profile by preventing the neuroleptic-induced EPS and might be a better alternative during its long period of psychiatric treatment over conventional dosage form.
Department of Pharmaceutics, J. S. S. College of Pharmacy, Rocklands, Ooty, Tamil Nadu State, India. samanta@md5.vsnl.net.in
M K
MK
Samanta
R
R
Dube
B
B
Suresh
D000279:Administration, Cutaneous; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006207:Half-Life; D006220:Haloperidol / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D051379:Mice; D011817:Rabbits; D051381:Rats; D012559:Schizophrenia / Q000188:drug therapy*
D014150:Antipsychotic Agents; D006220:Haloperidol