Design of a transdermal delivery system for aspirin as an antithrombotic drug.
Aspirin has become the gold standard to which newer antiplatelet drugs are compared for reducing risks of cardiovascular diseases, while keeping low cost. Oral aspirin has a repertoire of gastrointestinal side effects even at low doses and requires high frequent dosing because it undergoes extensive presystemic metabolism. Transdermal delivery offers an alternative route that bypasses the gut and may be more convenient and safer for aspirin delivery especially during long-term use. This study comprised formulation of aspirin in different topical bases. Release studies revealed that hydrocarbon gel allowed highest drug release. In vitro permeation studies revealed high drug permeation from hydrocarbon gel. Several chemical penetration enhancers were monitored for augmenting the permeation from this base. Combination of propylene glycol and alcohol showed maximum enhancing effect and, hence, was selected for biological investigation. The biological performance of the selected formulation was assessed by measuring the inhibition of platelet aggregation relevant to different dosage regimens aiming to minimize both drug dose and frequency of application. The results demonstrated the feasibility of successfully influencing platelet function and revealed that the drug therapeutic efficacy in transdermal delivery system is dose independent. Biological performance was re-assessed after storage and the results revealed stability and persistent therapeutic efficacy.
Ammar
H O
HO
Department of Pharmaceutical Sciences, National Research Center, Dokki, Cairo, Egypt. husseinammar@hotmail.com
Ghorab
M
M
El-Nahhas
S A
SA
Kamel
R
R
D000279:Administration, Cutaneous; D000818:Animals; D001241:Aspirin / Q000008:administration & dosage* / Q000737:chemistry*; D002266:Carboxymethylcellulose Sodium / Q000008:administration & dosage / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003505:Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry; D004121:Dimethyl Sulfoxide / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems; D004355:Drug Stability; D004356:Drug Storage; D005233:Fatty Alcohols / Q000008:administration & dosage / Q000737:chemistry; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000737:chemistry*; D066298:In Vitro Techniques; D008297:Male; D008899:Mineral Oil / Q000008:administration & dosage / Q000737:chemistry; D009226:Myristates / Q000008:administration & dosage / Q000737:chemistry; D010577:Petrolatum / Q000008:administration & dosage / Q000737:chemistry; D010974:Platelet Aggregation / Q000187:drug effects; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption / Q000187:drug effects; D012967:Sodium Dodecyl Sulfate / Q000008:administration & dosage / Q000737:chemistry; D014508:Urea / Q000008:administration & dosage / Q000737:chemistry
D003505:Cyclodextrins; D005233:Fatty Alcohols; D005343:Fibrinolytic Agents; D009226:Myristates; C009316:stearyl alcohol; D012967:Sodium Dodecyl Sulfate; D011092:Polyethylene Glycols; D010577:Petrolatum; D008899:Mineral Oil; D014508:Urea; D002266:Carboxymethylcellulose Sodium; D001241:Aspirin; D004121:Dimethyl Sulfoxide