Terbutaline Transdermal Delivery: Preformulation Studies and Limitations of In-vitro Predictive Parameters

Abstract

A transdermal dosage form of terbutaline may be useful to prevent nocturnal wheezing by providing prolonged duration of action. It will also improve patient compliance and bioavailability. Controlled input of the drug would be an additional advantage as this will reduce the intersubject variability. Preformulation studies were conducted to determine the feasibility of a transdermal dosage form of terbutaline. The drug solubility in propylene glycol was 6.3 mg mL-1. The apparent partition coefficient (n-octanol/ deionized-water, pH 6.5) of terbutaline was 0.03. A pH-partition coefficient (octanol/buffer) profile indicated that the partition coefficient values were 0.02, 0.05 and 0.4 in buffers of pH 3, 7.4 and 9, respectively. The required drug flux through the human skin to attain therapeutic concentrations in the blood was calculated to be 3.3 micrograms cm-2 h-1 for a 10-cm2 transdermal delivery system. Rabbit, guinea-pig and human skin was tested as the penetration barrier using modified Franz diffusion cells. Terbutaline flux values through the rabbit and guinea-pig skin were 8.3 and 7.7 micrograms cm-2 h-1, respectively. The flux through human full-thickness skin and human epidermis were 0.6 and 3.6 micrograms cm-2 h-1. Azone (3% w/v), a skin penetration enhancer, significantly increased the drug flux through all the membranes tested. Based on these studies, transdermal delivery of terbutaline appears to be promising.

Prodrug Strategies for Enhancing the Percutaneous Absorption of Drugs

“…In order to study and determine the partition coefficient of a drug, organic solvents are used to mimic the different phases/domains that a molecule must cross to enter the systemic circulation. The n -octanol-water partition coefficient (log P) is a good representation of the partitioning of a drug in between the lipophilic SC and the underlying hydrophilic living cells of the epidermis [33]. The log D value (the log P value at a specific pH) of a compound is usually a good indication as to whether a molecule would be a favorable candidate for transdermal permeation, or not.…”

Comparative study of hair follicle morphology in eight mammalian species and humans

“…Comparing rates of absorption, porcine skin resembles human skin like no other species' skin with only slightly increased penetration rates for porcine skin (23,25,26). Compared with the human and porcine skin, most studies reveal vastly higher absorption rates in Guinea pigs, rats, mice, and rabbits (25,(27)(28)(29). The skin permeability of dogs and cats was investigated by Marzulli et al (27) and McGeesh (30).…”

Artificial neural network analysis for predicting human percutaneous absorption taking account of vehicle properties

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