Effect of Sucrose Fatty Acid Esters on Transdermal Permeation of Lidocaine and Ketoprofen

Abstract

Skin has many advantages as a site for local and systemic drug administration. However, the barrier properties of the outermost layer, the stratum corneum, have limited the number of successful transdermal dosage forms developed thus far. One of the strategies for overcoming this problem is temporary local reduction of the barrier function of the stratum corneum with the aid of a percutaneous absorption enhancer.Sucrose fatty acid esters (sugar esters) are nonionic surfactants with sucrose as the polar head group and one or several fatty acid chains as the lipophilic moiety. Some of them are legally approved as food additives due to their high safety 1) and are registered as pharmaceutical excipients in Japan, USA, Canada, Australia, and New Zeeland.2) Sugar esters have low irritancy to the skin and eyes. 1) There have been several reports or patents about utilizing sugar esters as additives for drug formulations. Some sugar esters enhance gastrointestinal absorption of elastase 3) and blactam antibiotics.4) The nasal mucosal absorption of peptides such as calcitonin, 5) interferon, 6) and a-human atrial natriuretic polypeptide 7) are increased by sucrose laurate or sucrose stearate. Sucrose palmitate enhances the absorption of calcitonin from the oral mucosa 8) and gingiva 9) in rats. Ganem-Quintanar et al. examined the effect of sucrose stearate, oleate, palmitate, and laurate on the permeation of lidocaine hydrochloride through excised pig palate and cheek and reported that only sucrose laurate acted as an absorption enhancer.10) Some sugar esters act as percutaneous absorption enhancers. It has been reported that sucrose stearate and sucrose laurate increase percutaneous absorption of bromhexine in rats 11) and oestradiol in rabbits, 12) respectively. The percutaneous absorption of diltiazem and hydromorphone are also aided by some sugar esters. 13,14) Nakada et al. examined the effect of more than 10 sugar esters with HLB ranging 2 to 16 on the absorption of calcitonin from oral mucosa in rats.8) An enhancing effect was found for sugar esters with HLB values ranging from 11 to 16. However, the effect of the length of the fatty acid chain and HLB of sugar esters on their activity as percutaneous absorption enhancers has not been reported.In the present study, we selected six sugar esters with HLB 5-16 and evaluated their effect on percutaneous drug permeation in in vitro experiments using excised hairless mouse skin. We employed lidocaine (LC, pK a ϭ7.9) 15) and ketoprofen (KP, pK a ϭ4.0) 16) as model basic and acidic drugs, respectively. The drugs were dissolved in buffer solutions with several pHs so that we could evaluate the effect of the sugar esters on the percutaneous permeation of ionized and unionized drug species.It has been reported that sugar esters form micelles in water and in an organic solvent.17) The micelles would affect the thermodynamic properties of a penetrant in a vehicle. To examine the effect of sugar esters on skin permeability and to minimize the effect on vehicle or interaction wi...

Development of Novel Fast-Disintegrating Tablets by Direct Compression Using Sucrose Stearic Acid Ester as a Disintegration-Accelerating Agent

“…In this study, SSE with an HLB of 16 (S-1670) was used because it exhibited good wettability. However, as there are other kinds of sucrose fatty acid esters, 25,26) their possibility as a disintegration-accelerating agent might have to be studied in the future. Furthermore, automatic compression with a single stroke press or rotary press will have to be examined for practical use in the future.…”

Efficient Delivery and Distribution in Skin of Chlorogenic Acid and Resveratrol Induced by Microemulsion Using Sucrose Laurate

“…6) Sucrose fatty acid esters have also been shown to work as percutaneous penetration enhancers for some drugs, such as lidocaine hydrochloride, 20) lidocaine and ketoprofen, 21) and ibuprofen. 22) However, skin penetration studies using sucrose fatty acid ester microemulsions have yet to be performed adequately.…”

Effect of Penetration Enhancers on Transdermal Delivery of Propofol

“…Recently, sucrose fatty acid esters have attracted attention as enhancers for transdermal delivery. 13) From these results, PF solutions containing membrane-acting type enhancers showed higher values than that of 100% PF, and 10 and 15% (w/w) LIM showed the highest values. Figure 5 and Table 3 show the cumulative amount permeated-time profiles and permeation parameters after application of PF solutions containing co-solvent type enhancers.…”

“…The membrane-acting types, such as fatty acid, 5-7) terpene [8][9][10] and surfactant, [11][12][13] achieve effects using small amounts by altering the condition of the lipid membrane constituting the stratum corneum. The co-solvent types, such as propylene glycol (PG), 10,14) polyethylene glycol 15) and ethanol, 8) achieve effects by improving the solubility of drugs or enhancing permeation of drugs through the skin.…”