Development of diatomite-chitosan composites and evaluation as a drug release system

Controlled drug release systems are systems that keep the active substance concentration in the long-term therapeutic range. Thus, it is aimed to reduce the dosing frequency, increase the effectiveness of the drug, and eliminate or minimize possible side effects if possible. Micro- and nano-scale drug release systems have greatly influenced the pharmaceutical industry by minimizing the disadvantages such as short plasma half-life of the active substance, poor stability, and side effects. In recent years, porous silica-based micro and nanostructures have attracted interest in pharmaceutical applications. Diatomaceous earth, known as diatomite, is a fossil material of sedimentary origin formed over centuries by the siliceous skeletons of single-celled microalgae in water found at the bottom of lakes or marine environments. In this study, the enrichment of diatomite, which is an industrial raw material, and its evaluation as a drug release system were investigated. In the first stage of the study, the diatomite obtained from the Seyçiler/Afyonkarahisar region was purified by appropriate enrichment techniques. For this, diatomite with reduced grain size was calcined. Then, the loading (absorption) performances of Diphenhydramine Hydrochloride (DPH), an antihistamine active ingredient, on diatomite-chitosan composites were investigated. After DPH loading studies were completed, DPH release profiles (desorption) and release kinetics from composites were investigated. In vitro release profiles were studied at 37 °C ambient temperature and time vs. stomach medium (pH: 1.2). For this, the USB apparatus 1 method (basket method) was used. In addition, the diatomite sample was characterized by XRD, XRF, FTIR, BET-BJH, SEM-EDX, particle size distribution, zeta potential tests. According to the results obtained, it was determined that the diatomite consisted of amorphous silica. After enrichment, the surface area is 21.69 m2/g for natural diatomite and 75.11 m2/g for calcined diatomite. Total pore volumes are 0.24 cm3/g and 0.76 cm3/g for natural and calcined diatomite, respectively. It was observed that the mean pore diameters decreased by 6% as a result of the calcination process. When the particle size distribution of the calcined diatomite was examined, it was determined that 90% of it was smaller than 21.3 µm. As is known, the negative surface charge of the diatomite in the wide pH range was proved once again by zeta potential measurements. The highest loading capacity was calculated as 91.13 mg/g and the lowest loading capacity was calculated as 48.75 mg/g in the prepared DPH loaded formulations. Capsule formulations were preferred for in vitro release studies. According to the results obtained, it was observed that the diatomite-chitosan composite released 90% of the drug in a controlled manner for 60 minutes and remained in harmony with the Higuchi kinetics.