Hydroxypropylmethylcellulose films for prolonged delivery of the antipsychotic drug chlorpromazine.
OBJECTIVE
The aim of this study was to develop transdermal films based on hydroxypropylmethylcellulose with the purpose of improving transdermal permeation of chlorpromazine hydrochloride, an antipsychotic drug used to alleviate the symptoms and signs of psychosis.


METHODS
Hydroxypropylmethylcellulose films were prepared and evaluated for their drug content, film thickness, residual water content and bioadhesive properties. In-vitro permeation experiments were performed in the absence and in the presence of permeation enhancers (oleic acid, polysorbate 80, or both) with the purpose of improving drug availability. Other formulative parameters, such as drug and plasticizer concentration and hydroxypropylmethylcellulose type, were investigated.


RESULTS
Both oleic acid and polysorbate 80 had significant effect on drug permeation with respect to the control formulation. In particular films containing a mixture of oleic acid and polysorbate 80 provided the best enhancement activity for chlorpromazine. Moreover, a decrease in propylene glycol or chlorpromazine content or an increase of hydroxypropylmethylcellulose viscosity provided lower cumulative amounts of drug permeated.


CONCLUSIONS
The results obtained confirm that chlorpromazine permeation can be easily modulated by varying the composition of hydroxypropylmethylcellulose-based films. These formulations could serve as candidates for transdermal delivery of antipsychotic drugs.
Luppi
Barbara
B
Department of Pharmaceutical Sciences, Bologna University, Bologna, Italy.
Bigucci
Federica
F
Baldini
Mattia
M
Abruzzo
Angela
A
Cerchiara
Teresa
T
Corace
Giuseppe
G
Zecchi
Vittorio
V
D000268:Adhesiveness; D000279:Administration, Cutaneous; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D002746:Chlorpromazine / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics; D005079:Excipients / Q000737:chemistry*; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D019301:Oleic Acid / Q000737:chemistry; D009994:Osmolar Concentration; D010539:Permeability; D010968:Plasticizers / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry; D019946:Propylene Glycol / Q000737:chemistry; D012867:Skin / Q000378:metabolism; D013501:Surface-Active Agents / Q000737:chemistry; D034421:Sus scrofa; D014783:Viscosity; D014867:Water / Q000032:analysis
D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D005079:Excipients; D010968:Plasticizers; D011136:Polysorbates; D013501:Surface-Active Agents; D014867:Water; D019301:Oleic Acid; D065347:Hypromellose Derivatives; D019946:Propylene Glycol; D008747:Methylcellulose; D002746:Chlorpromazine