Tamoxifen Citrate Containing Topical Nanoemulgel Prepared by Ultrasonication Technique: Formulation Design and In Vitro Evaluation

The present study aims to design and develop a nanoemulgel formulation of Tamoxifen citrate (TAM), a water-insoluble, potent anticancer drug, using the spontaneous emulsification method to improve topical delivery, achieve high accumulation at the tumour site, and spare the healthy tissues. The oil-based selection was related to the TAM solubility, while the surfactant and co-surfactant were chosen based on the droplets’ thermodynamic stability and size. Afterwards, a pseudo-ternary phase diagram was built for the most promising formulation using two oils, olive and sesame, with a varied mix of Tween 40 as the surfactant and Transcutol HP as the co-surfactant (S_mix), by the optimisation of experiments. The nanoemulsion (NE) formulations that were prepared were found to have an average droplet size of 41.77 ± 1.23 nm and 188.37 ± 3.53 nm, with suitable thermodynamic stability and physicochemical properties. Both olive and sesame oils are natural food additives due to their associated antioxidant effects; therefore, they showed no toxicity profile on breast cell lines (MCF-7, ATCC number HTB-22). The TAM-NE preparations revealed a prolonged and doublings superior cumulative percentage of in vitro release of TAM compared to TAM plain gel suspension over 24 h. The release data suggested that the Higuchi model was the best fitting kinetical model for the developed formulations of NE1, NE9, and NE18. The extended release of the drug as well as an acceptable amount of the drug permeated TAM via nanogel preparations suggested that nanoemulgel (NEG) is suitable for the topical delivery of TAM in breast cancer management. Thus, this work suggests that a nanogel of TAM can improve anticancer properties and reduce systemic adverse effects compared to a suspension preparation of TAM when applied in the treatment of breast cancer.

See also Chapter 2.1 of the paper:

2.1 Screening of NEG Components—A Solubility Evaluation of TAM
It is important to examine the effects of different components’ behaviours when formulating NEs. High drug solubility in the oil phase is vital for developing an NE system as it permits the lipid carrier to encapsulate higher drug concentrations. The specific gravity and HLB value for the oil phase are also significant in the development of the NE system [20]. Figure 2 shows that the solubility of TAM was investigated in different oils and surfactants such as oleic acid, castor oil, olive oil, sesame oil, Tween 20, Tween 40, Tween 80, PEG 400, Transcutol HP, Kolliphore EL, triacetin, isopropyl myristate 98%, and Labrafac lipophile. From various studies on the components and the data available, the maximal solubility of TAM was found in olive and sesame oils, and in Tween 40 as a surfactant and in Transcutol HP as a co-surfactant. The high solubility in sesame and olive oil may be ascribed to the long-chain triglycerides, which helped in the maximal solubilisation of TAM [20,21]. However, Tween 40 exhibited maximum solubility compared to other examined surfactants, which are yellow to orange viscous liquids or pastes at room temperature, with a high HLB value of 15.6, which reflects high solubility in water, ethanol, methanol, ethyl acetate, and acetone. This can also be associated with molecular weight, as Tween 40 has a reduced particle size compared with other large polymeric surfactants. This can benefit the micellar solubilisation enhancement of the lipid drug in the oil phase and enables quicker emulsification efficiency to produce a fine NE system. Likewise, Transcutol HP revealed the highest solubility measurements for TAM. Transcutol HP is considered a very good co-surfactant and solubiliser for compounds that are hydrophobic and have low percutaneous transport [22]. Additionally, the use of Transcutol HP can be further attributed to an increase in the drug loading and fluidity of the preparation, which will be helpful in fast emulsification and attaining a small globule size [23].

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Alyami, M.H.; Alyami, H.S.; Alshehri, A.A.; Alsharif, W.K.; Shaikh, I.A.; Algahtani, T.S. Tamoxifen Citrate Containing Topical Nanoemulgel Prepared by Ultrasonication Technique: Formulation Design and In Vitro Evaluation. Gels 2022, 8, 456. https://doi.org/10.3390/gels8070456