Solutol HS-15 (Synonyms: Polyethylene glycol 12-hydroxystearate)

Solutol HS-15 , a clinically approved excipient, has neuroprotective properties^[1,2]. Solutol HS 15 (polyoxyethylene esters of 12-hydroxystearic acid) is non-ionic surfactant, with low toxicity in vivo, was shown to reverse completely the multidrug resistance of KB 8-5 and KB 8-5-11 human epidermoid carcinoma cells in vitro but did not potentiate drug toxicity in drug-sensitive KB 3-1 cells^[3]. Solutol HS-15 also acts as a permeability enhancer^[4].

Solutol HS 15 produced a 35-, 28-, and 42-fold reduction in the resistance of KB 8-5-11 cells to colchicine, vinblastine, and doxorubicin, respectively,at a concentration of 10% of its own IC₅₀ (mean concentration of drug that causes 50% inhibition of cell growth compared to controls). Like verapamil, Solutol HS 15 promoted a 50-fold accumulation of rhodamine 123 in KB 8-5-11 cells, as measured by flow cytometry. Also, Solutol HS 15 and verapamil reduced the efflux of rhodamine 123 from KB 8-5-11 cells previously loaded with rhodamine 123 to a similar low rate. Solutol HS 15 did not affect the transport of alanine or glucose into KB 8-5-11 cells, indicating that its effect upon membrane active transport is not entirely nonspecific.

Solutol HS 15 is a third generation surfactant carrier used to improve the solubility and bioavailability ^[5,6]. Solutol HS 15 was the most effective to increase the solubility of Pioglitazone HCl by approximately 33 fold whereas Cremophor RH 40 increased approximately 27 folds. Suitability of Solutol HS 15 has earlier been demonstrated with its physiological compatibility and safety ^[7].There was simultaneous increase in concentration of micelles along with increase in concentration of Solutol HS 15, because the concentration of Solutol HS 15 used in this study was higher than its critical micelle concentration ^[8]. This study revealed that Solutol HS 15 is an effective carrier in enhancing solubility and stability of the Pioglitazone HCl. ^[9]

Solutol HS 15 merits consideration as a potential therapeutic agent because of its effectiveness for reversing multidrug resistance in vitro and its low toxicity in vivo. With proper timing and dosage, administration of Solutol HS-15 can be an effective therapy against cerebral ischemia. Following ACA, the number of surviving hippocampal neurons was enhanced by Solutol-treated HS15 (68 %) rats as compared to ACA only-treated groups. Infarct volume was decreased by Solutol HS-15 (78 %) as compared to saline (vehicle) in MCAO-treated animals. Solutol HS-15 provide robust neuroprotection in both paradigms of ischemia. This may prove therapeutically beneficial since Solutol HS-15 is already administered as a solublizing agent to patients.

References:
[1]. Lin H W, Saul I, Gresia V L, et al. Fatty acid methyl esters and Solutol HS 15 confer neuroprotection after focal and global cerebral ischemia[J]. Translational stroke research, 2014, 5(1): 109-117.
[2]. Ku S, Velagaleti R. Solutol HS-15 as a novel excipient[J]. 2010.
[3]. Coon J S, Knudson W, Clodfelter K, et al. Solutol HS 15, nontoxic polyoxyethylene esters of 12-hydroxystearic acid, reverses multidrug resistance[J]. Cancer research, 1991, 51(3): 897-902.
[4]. Shubber S, et al. Mechanism of mucosal permeability enhancement of CriticalSorb? (Solutol? HS15) investigated in vitro in cell cultures. Pharm Res. 2015 Feb;32(2):516-27.
[5].Shamma RN, Basha M. Soluplus: A novel polymeric solubilizer for optimization of Carvedilol solid dispersions: Formulation design and effect of method of preparation. Powder Technol 2013;237:406-14.
[6].Song CK, Yoon IS, Kim DD. Poloxamer-based solid dispersions for oral delivery of docetaxel: Differential effects of F68 and P85 on oral docetaxel bioavailability. Int J Pharm 2016;507(1-2):102-8.
[7].Han HK, Lee BJ, Lee HK. Enhanced dissolution and bioavailability of biochanin A via the preparation of solid dispersion: In vitro and in vivo evaluation. Int J Pharm 2011;415(1-2):89-94.
[8].Bravo GonzÁlez RC, Boess F, Durr E, Schaub N, Bittner B. In vitro investigation on the impact of Solutol HS 15 on the uptake of colchicine into rat hepatocytes. Int J Pharm 2004;279(1-2):27-31.
[9]. Swain R P, Subudhi B B, Ramesh P. Effect of Solutol HS 15 in Solid Dispersions of Pioglitazone Hydrochloride: in vitro and in vivo Evaluation[J]. Indian Journal of Pharmaceutical Sciences, 2019, 81(2): 317-325.