The challenge of improving pterostilbene (PTS) solubility for solid and semi-solid dosage forms: The obtention of binary and ternary systems.

Pterostilbene (PTS) is a drug candidate with low water solubility and poor bioavailability. On the other hand, drug:cyclodextrins complexes frequently provide bulk powders with low drug concentrations, which is crucial for obtention solid or semi-solid pharmaceutical dosage forms. In order to determine the optimal conditions for enhancing the solubility of PTS:BCD (ß-cyclodextrin) complex, a Box-Behnken design was performed. Although the optimal conditions have been applied, low complexation efficiency (0.127) and the bulk powder remained. A PTS:BCD:HPMC (HPMC, hydroxypropyl methylcellulose) ternary system was developed to overcome this limitation, comparing two media, water and a mixture of ethanol-water. When ethanol was used as a co-solvent, the PTS:BCD:HPMC ternary system (freeze-dried) contained 116.65 ± 1.40 mg/g of PTS. This value was 3.4-fold higher than the PTS content observed when the same ternary system was obtained in aqueous media (34.8 mg/g) and 2.8-fold higher than the PTS content observed for PTS:BCD complex (freeze-dried) obtained using ethanol as a co-solvent. Dissolution tests revealed that after 120 min, in a buffer with a pH value of 1.2, only 43% of PTS dissolved. In contrast, 80% and 90% of PTS were dissolved from the PTS:BCD complex and PTS:BCD:HPMC ternary system, respectively. Moreover, the dissolution was fast in a buffer with a pH value of 6.8. PTS:BCD complex reached the maximum PTS dissolution at 75 min and PTS:BCD:HPMC at 45 min. In summary, the results of this study demonstrated, for the first time, that low-bulk powders with a high content of PTS can be obtained from PTS:BCD:HPMC ternary systems using ethanol as a co-solvent. This new finding offers a valuable alternative for producing solid or semi-solid formulations containing highly soluble PTS.

Adipose tissue of female Wistar rats respond to Ilex paraguariensis treatment after ovariectomy surgery.

BACKGROUND AND AIM: Metabolic disturbances are known for their increasing epidemiological importance. Ilex paraguariensis presents a potential option for mitigating lipid metabolism imbalance. However, most of the literature to date has not considered sex bias. This study aimed to evaluate the effect of Ilex paraguariensis on the metabolism of different adipose tissue depots in males and females. EXPERIMENTAL PROCEDURE: After ovariectomy, female Wistar rats received daily treatment with the extract (1 g/kg) for forty-five days. Biochemical serum parameters and tissue metabolism were evaluated. Oxidation, lipogenesis and lipolysis were evaluated in brown, white visceral, retroperitoneal and gonadal adipose tissues. RESULTS AND CONCLUSION: The results showed that treatment with the extract led to a reduced weight gain in ovariectomised females in comparison to control. The triglyceride concentration was decreased in males. Glucose oxidation and lipid synthesis in visceral and retroperitoneal adipose tissues were restored in ovariectomised females after treatment. The response to epinephrine decreased in visceral adipose tissue of control males; however, lipolysis in females did not respond to ovariectomy or treatment. These findings highlight the enormous potential effects of I. paraguariensis on lipid metabolism, modulating lipogenic pathways in females and lipolytic pathways in males. Furthermore, the sex approach applied in this study contributes to more effective screening of the effects of I. paraguariensis bioactive substances.

Development and validation of a specific-stability indicating liquid chromatography method for quantitative analysis of pterostilbene: application in food and pharmaceutical products.

Pterostilbene is a natural constituent with numerous preventive and therapeutic properties used for treating a wide range of human diseases. It has been isolated from blueberries in high concentrations. A versatile specific-stability indicating liquid chromatography method for reliable quantitative determination of pterostilbene in blueberry extracts was developed. In the stability-indicating analysis, pterostilbene samples were exposed to stress conditions: temperature, UV light, and oxidative, acid and alkaline media. The robustness of the method was evaluated using a Box-Behnken experimental design. Pterostilbene was stable in acid and alkaline media, but unstable when exposed to oxidation, high temperature, and UV light. Using the proposed method, it was demonstrated that degradation products did not interfere in the analyte analysis. The method revealed to be simple, fast, selective, linear, precise and accurate for the quantitative analysis of pterostilbene in Vaccinium myrtillus extract. Besides being a specific-stability indicating method, it demonstrated to be applicable to quantify pterostilbene in pterostilbene:ß-cyclodextrin complexes and pterostilbene:ß-cyclodextrin:hydrophilic polymer ternary systems. These findings are relevant for the development of food, pharmaceutical or cosmetic products containing pterostilbene or blueberry extracts.