Porous Microparticles Containing Raloxifene Hydrochloride Tailored by Spray Freeze Drying for Solubility Enhancement

• Published in: Advanced pharmaceutical bulletin 2018-06, Vol.8 (2), p.217-223
• Main Authors: Hadipour Moghaddam, Seyyed Pouya, Farhat, Sajjad, Vatanara, Alireza
• Format: Article
• Language: English
• Subjects: Bioavailability; Breast cancer; Dissolution profile; Drugs; Fourier transforms; Methods; Nitrogen; Pharmaceuticals; Porous microparticles; Raloxifene; Scanning electron microscopy; Solubility; Spectrum analysis; Spray freeze drying
• ISSN: 2228-5881; 2251-7308
• DOI: 10.15171/apb.2018.026

[...]Raloxifene has been approved for the prevention of osteoporosis as well as reducing the risk of invasive breast cancer in postmenopausal women.1 RH shows very low oral bioavailability (c.a. 2% of the given dose) which is mostly due to its extensive first pass hepatic metabolism via glucuronide conjugation as well as incomplete dissolution as the drug is poorly water-soluble.2,3 This drug is categorized as class II of Biopharmaceutical Classification System (BCS).4 Accordingly, its low bioavailability seems to be enhanced by increasing its solubility.5,6 Several techniques can be used to improve solubility of drugs such as co-grinding, salt formation, spray drying, and supercritical fluid processing.7-10 In order to increase the solubility of RH, different methods have been investigated to date. Co-grinding of RH with different superdisintegrants such as polyvinylpyrrolidone (PVP), hydroxypropylmethyl cellulose, crospovidone, croscarmellose sodium, and sodium starch glycolate have been reported and resulted in considerable improvement of drug solubility in most cases.7,11 Spray freeze drying (SFD) is relatively a novel technique for pharmaceutical particle engineering and drying of foods as well as bioproducts.12,13 In this process, a feed solution is atomized by a nozzle over/in a cryogenic medium and frozen droplets are lyophilized in low pressure and temperature. Many factors can influence particle characteristics produced by this method such as composition, total solid content of liquid feed solution, spraying rate of liquid feed, distance between nozzle, and cryogenic liquid surface.15,16 In the present study, the effect of SFD method on dissolution rate of RH was studied in the presence of PVP and HPßCD as solubility enhancers. Approximately, 5 mg of the samples were sealed firmly and scanned under dry nitrogen atmosphere at the heat rate of 10 °C per minute from 10 to 350 °C. Scanning Electron Microscopy (SEM) A Philips Model XL30 scanning electron microscope (Philips, The Netherlands) was used to obtain the SEM images.