Infant formula as a solid lipid dose form for enhancement of the oral bioavailability of cannabidiol for paediatric patients.

Cannabinoids can save paediatric patients from harmful psychological conditions caused by epilepsy. However, the limited aqueous solubility of the drug presents a limitation to oral absorption and bioavailability. Previous studies have shown the enhancement of oral bioavailability for poorly water-soluble drugs using milk or milk-based products like infant formula as a novel lipid-based formulation, due to digestion of the lipids to enhance drug solubility that is particularly well suited to infants and in low economy settings. Therefore, this study has investigated the in vitro solubilisation enhancement of cannabidiol (CBD) in milk-based products during digestion using synchrotron small angle X-ray scattering, followed by pharmacokinetic studies to determine the relative oral bioavailability. The in vitro results, coupled with in vivo data, demonstrate a two-fold increase in the oral bioavailability of CBD in bovine milk as well as infant formula. The results of this study indicate the potential for infant formula to be considered as a novel formulation approach for CBD. Further study is encouraged for more drugs with infant formula to strengthen the correlation between the solubilisation of drug and their oral bioavailability.

Revisiting the Dissolution of Praziquantel in Biorelevant Media and the Impact of Digestion of Milk on Drug Dissolution.

Praziquantel is a poorly water-soluble drug used to treat parasitic infections. Previous studies have suggested that its rate and extent of dissolution in milk and biorelevant media are slow and limited compared to dissolution in the pharmacopoeial-recommended medium, despite being reported as displaying a positive food effect upon administration. This study aimed to revisit the dissolution of praziquantel in biorelevant media and milk to better understand this apparent dichotomy. The context of digestion was introduced to better understand drug solubilisation under more relevant gastrointestinal conditions. The amount of praziquantel solubilised in the various media during digestion was quantified using high performance liquid chromatography (HPLC) and the kinetics of dissolution were confirmed by tracking the disappearance of solid crystalline drug using in situ small angle X-ray scattering (SAXS). For the dissolution media, where sodium lauryl sulfate (SLS) is typically included as a wetting agent, a prominent effect of SLS on drug dissolution was also apparent where >2.5 fold more drug was solubilised in SLS-containing dissolution medium compared to that without (0.1 M HCl only). In milk, significant dissolution of praziquantel was observed only during digestion and not during dispersion, hence suggesting that (1) milk can be potentially administered with praziquantel to improve oral bioavailability and (2) incorporating a digestion step into existing in vitro dissolution testing can better reflect the potential for a positive food effect when lipids are present.

Opportunities for milk and milk-related systems as 'new' low-cost excipient drug delivery materials.

Milk is well recognised as an amazing delivery system for essential lipids, poorly soluble nutrients, sugars, amino acids and delivery of critical biological molecules to sustain the infant and adult alike. It is also a safe and abundant resource with potential to act as a low-cost material for formulation of medicines, especially for paediatric patients and those in low economy settings. However, its use in low cost formulations has never developed beyond preclinical evaluation. Reasons for this are several-fold including variable composition and therefore regulatory challenges, as well as a lack of clear understanding around when milk or milk-related materials like infant formula could best be deployed by linking drug properties with excipient composition attributes, especially when taking digestion into account. This review collects the current understanding around these issues. It is apparent from the evolving understanding that while milk may be a bridge too far for translation as an excipient, infant formula is positioned to play a key role in the future because, as a powder-based excipient, it has the performance benefits of milk powder together with the controlled specifications during manufacture and versatility of application to function as a low cost lipid excipient to enable potential translation for the oral delivery of poorly water soluble drugs for key populations including paediatrics and low economy medicines.

Effectiveness of a regional corridor in connecting two Florida black bear populations.

Corridors may mitigate the adverse effects of habitat fragmentation by restoring or maintaining connectivity between disjunct populations. The efficacy of corridors for large carnivores, however has rarely been evaluated objectively. We used noninvasive sampling, microsatellite analysis, and population assignment tests to evaluate the effectiveness of a regional corridor in connecting two Florida black bear (Ursus americanus floridanus) populations (Osceola and Ocala). Bear movement was predominantly unidirectional, with a limited mixing of individuals from the two populations in one area of the corridor We also documented bears in Osceola that were genetically assigned to Ocala and bears in Osceola that may be offspring from an Osceola-Ocala mating. Our results indicate that the Osceola-Ocala corridor is functional and provides a conduit for gene flow between these populations. Human development, however may hinder the use of the Osceola-Ocala corridor by bears. The noninvasive sampling and genetic methods we used provide a means of evaluating corridor effectiveness that can help identify linkages necessary for maintaining metapopulation structure and population viability.

Analysis of the bite force and mechanical design of the feeding mechanism of the durophagous horn shark Heterodontus francisci.

Three-dimensional static equilibrium analysis of the forces generated by the jaw musculature of the horn shark Heterodontus francisci was used to theoretically estimate the maximum force distributions and loadings on its jaws and suspensorium during biting. Theoretical maximum bite force was then compared with bite forces measured (1) voluntarily in situ, (2) in restrained animals and (3) during electrical stimulation of the jaw adductor musculature of anesthetized sharks. Maximum theoretical bite force ranged from 128 N at the anteriormost cuspidate teeth to 338 N at the posteriormost molariform teeth. The hyomandibula, which connects the posterior margin of the jaws to the base of the chondrocranium, is loaded in tension during biting. Conversely, the ethmoidal articulation between the palatal region of the upper jaw and the chondrocranium is loaded in compression, even during upper jaw protrusion, because H. francisci's upper jaw does not disarticulate from the chondrocranium during prey capture. Maximum in situ bite force averaged 95 N for free-swimming H. francisci, with a maximum of 133 N. Time to maximum force averaged 322 ms and was significantly longer than time away from maximum force (212 ms). Bite force measurements from restrained individuals (187 N) were significantly greater than those from free-swimming individuals (95 N) but were equivalent to those from both theoretical (128 N) and electrically stimulated measurements (132 N). The mean mass-specific bite of H. francisci was greater than that of many other vertebrates and second highest of the cartilaginous fishes that have been studied. Measuring bite force on restrained sharks appears to be the best indicator of maximum bite force. The large bite forces and robust molariform dentition of H. francisci correspond to its consumption of hard prey.