Novel Strategies for Solubility and Bioavailability Enhancement of Bufadienolides

Toad venom contains a large number of bufadienolides, which have a variety of pharmacological activities, including antitumor, cardiovascular, anti-inflammatory, analgesic and immunomodulatory effects.. The strong antitumor effect of bufadienolides has attracted considerable attention in recent years, but the clinical application of bufadienolides is limited due to their low solubility and poor bioavailability. In order to overcome these shortcomings, many strategies have been explored, such as structural modification, solid dispersion, cyclodextrin inclusion, microemulsion and nanodrug delivery systems, etc. In this review, we have tried to summarize the pharmacological activities and structure–activity relationship of bufadienolides. Furthermore, the strategies for solubility and bioavailability enhancement of bufadienolides also are discussed. This review can provide a basis for further study on bufadienolides.

Oral Bioavailability Enhancement of Melanin Concentrating Hormone, Development and In Vitro Pharmaceutical Assessment of Novel Delivery Systems

The rapid progress in biotechnology over the past few decades has accelerated the large-scale production of therapeutic peptides and proteins, making them available in medical practice. However, injections are the most common method of administration; these procedures might lead to inconvenience. Non-invasive medications, such as oral administration of bio-compounds, can reduce or eliminate pain and increase safety. The aim of this project was to develop and characterize novel melanin concentrating hormone (MCH) formulations for oral administration. As a drug delivery system, penetration enhancer combined alginate beads were formulated and characterized. The combination of alginate carriers with amphiphilic surfactants has not been described yet. Due to biosafety having high priority in the case of novel pharmaceutical formulations, the biocompatibility of selected auxiliary materials and their combinations was evaluated using different in vitro methods. Excipients were selected according to the performed toxicity measurements. Besides the cell viability tests, physical properties and complex bioavailability assessments were performed as well. Our results suggest that alginate beads are able to protect melanin concentrating hormones. It has been also demonstrated that penetration enhancer combined alginate beads might play a key role in bioavailability improvement. These formulations were found to be promising tools for oral peptide delivery. Applied excipients and the performed delivery systems are safe and highly tolerable; thus, they can improve patients’ experience and promote adherence.

BIOAVAILABILITY ENHANCEMENT BY FLOATING MICROBALLOONS OF DIPYRIDAMOLE AND CLOPIDOGREL: IN VIVO PHARMACOKINETIC STUDY

Objective: In vivo pharmacokinetic studies of clopidogrel and dipyridamole floating microballoons to check their bioavailability enhancement. Methods: The bioanalytical method development was carried by using HPLC with column Poroshell 120 EC-C 18; 4.6x100 mm. The in vivo pharmacokinetic studies were performed in Wistar male rats and the obtained data from the pharmacokinetic parameters were analyzed using PK Solver software. Results: The developed bioanalytical method was found to be linear in the concentration range of 1-100 ng/ml for clopidogrel bisulfate and 0.02-4µg/ml for dipyridamole with correlation coefficient of 0.9993 and 0.9987 respectively. The study results showed that the method was simple, linear, accurate and precise. The in vivo studies indicated that the AUC was found to be increased by 33.3% and 154.5% for clopidogrel and dipyridamole micro balloons, respectively, when compared to their pure drugs. Conclusion: The bioanalytical methods development and their validation parameters indicated that the methods are accurate, precise and linear in the studied range of concentrations. In vivo test results infer to the effective, sustained release of both the drugs when formulated as micro balloons and increase in the absorption, thereby enhancing the bioavailability of the drugs. The pharmacokinetic studies also confirmed the increase in the mean residence time of the drugs when formulated as floating microballoons.