ORIGINAL ARTICLE Enhancement of Fingolimod Content Uniformity as a Low-Dose Drug with Narrow Therapeutic Index Using Liquisolid Technique Tahereh Sobhani 1 & Javad Shokri 2 & Yousef Javadzadeh 2 # Springer Science+Business Media, LLC, part of Springer Nature 2020 Abstract Purpose Acceptable content uniformity is one of the major challenges in industrial pharmacy especially in low-dose drugs with narrow therapeutic index. Several methods have been proposed for solving this problem. Liquisolid technique is a new promising method that mainly has been used for enhancing solubility rate of drugs. It seems that this method could be able to obtain better distribution of drug and then content uniformity. The purpose of this investigation was to improve content uniformity of fingolimod hydrochloride, which is a low-dose drug with narrow therapeutic index, using liquisolid technique. Methods In this study, liquisolid formulations were prepared using PG as nonvolatile solvent and also absolute ethanol as a volatile solvent. The analysis carried out using HPLC method and content uniformity test was done according to the USP guideline. Results The results showed that content uniformity was improved in liquisolid method in comparison with classic method. Better distribution was obtained using combination of nonvolatile and volatile solvents. Conclusion It seemed that liquisolid method could be used as a promising technique for obtaining acceptable content uniformity in low-dose drugs with narrow therapeutic index such as fingolimod hydrochloride. Keywords Fingolimod hydrochloride . Liquisolid . Content uniformity . Drug formulation Introduction Fingolimod hydrochloride is a new drug used in the treatment of various autoimmune diseases and multiple sclerosis. Fingolimod is synthesized in the form of hydrochloride salts, which is completely soluble in water. Its chemical name is 2- amino-2-[2-(4-octylphenyl)ethyl]-1,3-propanediol hydrochlo- ride. The chemical formula of this drug is C19H33NO2 • HCl. Its molecular weight as a basic form and a salt form is 343.93 and 307.48, respectively [1]. Fingolimod hydrochlo- ride does not contain chiral carbon, so it does not show any specific rotation [2]. However, this drug is available in three distinct polymorphic forms, which are obtained in various temperatures [3]. Moreover, Fingolimod hydrochloride is used in adult pa- tients with recurrent multiple sclerosis to reduce the frequency of relapses and delay the progression of disability. It is a mod- ulator of the sphingosine-1-phosphate receptor, which is me- tabolized in the body by the sphingosine kinase enzyme to the active metabolite of fingolimod phosphate, an antagonist of SIP receptors on lymphocytes, which prevents lymphocytes from leaving the lymph nodes. This, in turn, reduces the infil- tration of pathogenic lymphocytes into the central nervous system, where lymphocytes could cause inflammation and destruction of the nervous tissue. The biggest challenge in the formulation of this drug is its content uniformity in the dosage forms. In the market, in each capsule of the fingolimod hydrochloride, there is only 0.5 mg of drug in a total content of 250 mg, which is about 0.2% of the total content. Therefore, uniform distribution of an active ingredient in granules and capsules is very important. In case of uneven distribution, each capsule would be filled by differ- ent amounts of the active ingredient and consequently irrepa- rable side effects and harm would occur for the patients. Accordingly, it is important to use a reliable industrial produc- tion method with the ability to distribute the drug uniformly. * Yousef Javadzadeh javadzadehy@yahoo.com; javadzadehy@tbzmed.ac.ir 1 Student Research Committee, Tabriz University of Medical Science, Tabriz, Iran 2 Biotechnology Research Center, Tabriz University of Medical Sciences, Daneshgah Street, Tabriz, Iran Journal of Pharmaceutical Innovation https://doi.org/10.1007/s12247-020-09492-8