The effect of permeation enhancers on the viscosity and the release profile of transdermal hydroxypropyl methylcellulose gel formulations containing diltiazem HCl.
METHODS
The objective of this study was to characterize the release of Diltiazem HCl (DTM HCl) from hydroxypropyl methylcellulose gels containing the following permeation enhancers at a 0.5% (w/w): sodium lauryl sulfate, dimethyl sulfoxide (DMSO), polysorbate 80, propylene glycol, N-methylpyrrolidone (NMP), fatty acids (oleic acid, caprylic acid, and myristic acid), and isopropyl myristate (IPM). The enhancers' effects on the gel's viscosity were also investigated.


RESULTS
The novel findings of this study were the following: (i) polysorbate 80 was used for the first time as an enhancer with a hydrophilic compound in a hydrophilic carrier and it rendered the highest permeation flux (57.1 +/- 0.9 microg/cm(2)/h) compared with the rest of the enhancers, (ii) myristic acid (a 14-carbon-chain fatty acid) rendered the highest permeation flux (18.4 +/- 0.49 microg/cm(2)/h) among all fatty acids because of a decrease in the gel's viscosity, (iii) NMP (46.5 +/- 0.7 microg/cm(2)/h) and IPM (15.3 +/- 0.41 microg/cm(2)/h) increased the permeation flux from the second day onward. Both enhancers increased the gel's viscosity, (iv) sodium lauryl sulfate decreased the viscosity of the gel and the drug's permeation flux (8.1 +/- 0.21 microg/cm(2)/h) because of its binding with the drug, (v) propylene glycol decreased the permeation flux (10.2 +/- 0.32 microg/cm(2)/h) by increasing the gel viscosity, and (vi) DMSO increased the permeation flux (13.8 +/- 0.4 microg/cm(2)/h) without altering the viscosity.


CONCLUSIONS
These findings indicate that to formulate DTM HCl into a hydroxypropyl methylcellulose gel the enhancers of choice should be polysorbate 80, myristic acid, DMSO, NMP, and IPM or combinations thereof.
Karakatsani
Marianthi
M
Division of Pharmaceutical Sciences, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY 11201, USA. marianthi_g_karakatsani@yahoo.com
Dedhiya
Mahendra
M
Plakogiannis
Fotios M
FM
D000279:Administration, Cutaneous; D002121:Calcium Channel Blockers / Q000737:chemistry* / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D004110:Diltiazem / Q000737:chemistry* / Q000493:pharmacokinetics*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005079:Excipients; D005227:Fatty Acids / Q000378:metabolism; D005782:Gels; D006801:Humans; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D010539:Permeability; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D012995:Solubility; D013678:Technology, Pharmaceutical; D014783:Viscosity
D002121:Calcium Channel Blockers; D004337:Drug Carriers; D005079:Excipients; D005227:Fatty Acids; D005782:Gels; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D004110:Diltiazem