A novel transdermal nanoethosomal gel of betahistine dihydrochloride for weight gain control: in-vitro and in-vivo characterization Shahira F El-Menshawe,1 Adel Ahmed Ali,1 Abdelkhalk Ali Halawa,2 Ahmed SG Srag El-Din2 1Department of Pharmaceutics and Industrial Pharmacy, Beni-Suef University, Beni-Suef, 2Department of Pharmaceutics and Clinical Pharmacy, Nahda University, Beni-Suef, Egypt Background: Betahistine dihydrochloride (BDH) is a histamine analog used to control weight gain, with short elimination half-life and gastric irritation as side effects.Objective: The aim of the current investigation is to formulate and optimize a topical BDH ethosomal gel for weight gain control.Materials and methods: Box–Behnken design was applied to study the effect of independent variables: phosphatidylcholine (PC), propylene glycol (PG), and ethanol on vesicle size; entrapment efficiency; % drug release; and flux. The morphology and zeta potential of the optimized formulation were evaluated. The % drug release, flux, and pharmacodynamics of the optimized formulation gel were studied.Results: The size and entrapment efficiency percent had a direct positive relationship with the concentration of PC and negative relationship with ethanol and PG. The % drug release and flux decreased with increasing PC and PG, while ethanol enhanced both responses. Regression modeling indicated a good correlation between dependent and independent variables, where F16 was chosen as the optimized formulation. F16 showed well-defined spherical vesicles and zeta potential of -24 mV, and % release from the gel exceeded 99.5% over 16 h with the flux of 0.28 mg/cm2/h. Food intake and weight gain of rats were significantly decreased after transdermal application of the BDH ethosomal gel when compared with control, placebo, and BDH gel. The histopathological findings proved the absence of inflammation and decrease in adipose tissue.Conclusion: Results obtained showed a significant, sustained transdermal absorption of BDH ethosomal gel and, consequently, a decrease in food intake and weight gain. Keywords: Box–Behnken design, regression modeling, neural histamine, pharmacodynamics, obesity

Purpose: This research aimed to improve water solubility and oral bioavailability of a newly synthesized thienopyrimidine derivative (TPD) with anti-pancreatic cancer activity by loading on starch nanoparticles (SNPs). Methods: TPD was synthesized, purified and its ADME behavior was predicted using Swiss ADME software. A UV spectroscopy method was developed and validated to measure TPD concentration at various dosage forms. SNPs loaded with TPD (SNPs-TPD) were prepared, characterized for particle size, polydispersity index, zeta potential, transmission electron microscopy, Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), entrapment efficiency, in-vitro release, and in-vivo animal study. Results: The Swiss ADME results showed that TPD can be administered orally; however, it has low oral bioavailability (0.55) and poor water solubility. The significant regression coefficient of the calibration curve (r² = 0.9995), the precision (%RSD < 0.5%) and the accuracy (99.46− 101.72%) confirmed the efficacy of the developed UV method. SNPs-TPD had a spherical monodispersed (PDI= 0.12) shape, nanoparticle size (22.98 ± 4.23) and good stability (− 21 ± 4.72 mV). Moreover, FT-IR and DSC revealed changes in the physicochemical structure of starch resulting in SNPs formation. The entrapment efficiency was 97% ± 0.45%, and the in-vitro release showed that the SNPs enhanced the solubility of the TPD. The in-vivo animal study and histopathology showed that SNPs enhanced the oral bioavailability of TPD against solid Ehrlich carcinoma. Conclusion: SNPs-TPD were superior in drug solubility and oral bioavailability than those obtained from TPD suspension.

The current work aimed at adopting in situ combination of sono-precipitation and alkali hydrolysis as a rapid technique for starch nanoparticles (SNPs) preparation under ambient conditions with a high yield. Factors affecting the preparation of SNPs were investigated based on statistical analysis using the Box Behnken design. The particle size and polydispersity index of particles were used as dependent variables to obtain the optimized formulation. The SNPs optimized formulation (F14) was further characterized for zeta potential, transmission electron microscopy, Fourier transform infrared spectroscopy, differential thermal analysis and X-ray diffraction. The results of particle size were between 44.82±3.31 and 83.93±8.53 while polydispersity index results were ranged from 0.106±0.012 to 0.179±0.018. The results obtained revealed the efficiency of the technique in obtaining a high yield (98.72% ±0.89) of well-distributed nanoparticles. Also, the SNPs obtained were spherical in shape with good stability, as indicated by zeta analysis (-20±0.25mV) and thermal analysis. The data obtained also showed no change in the chemical structure of the SNPs, as indicated by the infrared transmission of Fourier, thermal analysis, and the relative crystallinity of SNPs was decreased compared with native maize starch indicating the crystallite is transformed from crystalline to amorphous form. The obtained results concluded the efficiency of the adopted method on obtaining SNPs in a short preparation time with a high yield under ambient conditions.

Starch-based nanosystems are considered a talented nanocarrier for drug delivery owing to their small particle size, biodegradability, and biocompatibilities. Starch-based nanosystems showed enhancement in biological activity, solubility, entrapment efficiency, and in-vitro release of several drugs. Starch-based nanosystems are categorized into two types; starch nanocrystals and starch nanoparticles. The difference between starch nanocrystals and starch nanoparticles will be summarized. Numerous techniques are employed to formulate starch-based nanosystems including chemical and physical methods. This review summarizes the existing knowledge on; a number of techniques used to formulate starch-based nanosystems, factors affecting each technique, and the advantages of combining both physical and chemical methods on the formulation time and physicochemical properties of the starch-based nanosystems. Besides, most innovative information regarding starch-based nanosystems modification on increasing entrapment efficiency will be discussed. Furthermore, applying starch-based nanosystems as effective drug delivery nanocarriers for delivering drugs and bioactive elements to improve their bioavailability will be abridged in this review.