Enhanced Oral Bioavailability of ß-Caryophyllene in Healthy Subjects Using the VESIsorb® Formulation Technology, a Novel Self-Emulsifying Drug Delivery System (SEDDS).

ß-Caryophyllene (BCP), a common constituent of many spice and food plants, is gaining increased attention due to recent research identifying numerous potential health benefits. Due to limited oral bioavailability observed in preclinical models, the described benefits of BCP may be maximized by using a suitable delivery system. Additionally, human pharmacokinetics (PK) remain unknown. This study evaluates the relative oral bioavailability of BCP formulated in a self-emulsifying drug delivery system (SEDDS) based on VESIsorb® formulation technology (BCP-SEDDS) compared to BCP neat oil. Hence, a randomized, double-blind, cross-over design, single oral dose study (100 mg BCP) in 24 healthy subjects (12 men/12 women) was performed under fasting conditions. Pharmacokinetic parameters were analyzed from individual concentration-time curves. The data show that BCP-SEDDS resulted in a 2.2/2.0-fold increase in AUC0-12h/AUC0-24h and a 3.6-fold increase in Cmax compared to BCP neat oil. Moreover, BCP was absorbed faster from BCP-SEDDS (Tmax: 1.43 h) compared to BCP neat oil (Tmax: 3.07 h). Gender analysis revealed that there is no significant difference between men and women for both the investigated formulations and all investigated PK endpoints. In conclusion, BCP-SEDDS offers a well-tolerated and effective oral delivery system to significantly enhance the oral bioavailability of BCP in humans.

UC-II Undenatured Type II Collagen for Knee Joint Flexibility: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Study.

Objective: Joint-related stress models have been used in the past to induce a standardized load on physical structures, allowing researchers to observe changes in perceived stress on joints as accurately as possible in healthy individuals. Previous studies support the efficacy of UC-II® undenatured type II collagen ("undenatured collagen") supplementation in maintaining joint health. The purpose of this study was to assess the effect of undenatured collagen on knee flexibility in healthy subjects who experience activity-related joint discomfort (ArJD). Methods: This randomized, double-blind, placebo (PLA)-controlled study was conducted in healthy subjects with ArJD who had no history of osteoarthritis, or joint diseases. Ninety-six (n = 96, 20-55 years old) subjects who reported joint discomfort while performing a standardized single-leg-step-down test were randomized to receive either PLA (n = 48) or 40 mg of undenatured collagen (n = 48) supplementation daily for 24 weeks. Range of motion (ROM) flexion and extension were measured using a digital goniometer. Results: At the end of the study, a statistically significant increase in knee ROM flexion was observed in the undenatured collagen group versus the PLA group (3.23° vs. 0.21°; p = 0.025). In addition, an increase in knee ROM extension by 2.21° was observed over time in the undenatured collagen group (p = 0.0061), while the PLA group showed a nonsignificant increase by 1.27° (p > 0.05). Subgroup analysis by age showed a significant increase in knee ROM flexion in subjects >35 years old in the undenatured collagen supplemented group compared with PLA (6.79° vs. 0.30°; p = 0.0092). Conclusion: Overall, these results suggest that daily supplementation of 40 mg of undenatured collagen improved knee joint ROM flexibility and extensibility in healthy subjects with ArJD.

Evaluation and Validation of a Joint Stress Test to Induce Activity-Related Knee Joint Discomfort - a Prospective Case-Control Study.

BACKGROUND: The assessment of improvement or maintenance of joint health in healthy subjects is a great challenge. The aim of the study was the evaluation of a joint stress test to assess joint discomfort in subjects with activity-related knee joint discomfort (ArJD). RESULTS: Forty-five subjects were recruited to perform the single-leg-step-down (SLSD) test (15 subjects per group). Subjects with ArJD of the knee (age 22-62 years) were compared to healthy subjects (age 24-59 years) with no knee joint discomfort during daily life sporting activity and to subjects with mild-to-moderate osteoarthritis of the knee joint (OA, Kellgren score 2-3, age 42-64 years). The subjects performed the SLSD test with two different protocols: (I) standardization for knee joint discomfort; (II) standardization for load on the knee joint. In addition, range of motion (ROM), reach test, acute pain at rest and after a single-leg squat and knee injury, and osteoarthritis outcome score (KOOS) were assessed. In OA and ArJD subjects, knee joint discomfort could be reproducibly induced in a short time interval of less than 10 min (200 steps). In healthy subjects, no pain was recorded. A clear differentiation between study groups was observed with the SLSD test (maximal step number) as well as KOOS questionnaire, ROM, and reach test. In addition, a moderate to good intra-class correlation was shown for the investigated outcomes. CONCLUSIONS: These results suggest the SLSD test is a reliable tool for the assessment of knee joint health function in ArJD and OA subjects to study the improvements in their activities. Further, this model can be used as a stress model in intervention studies to study the impact of stress on knee joint health function.

A Novel Self-Emulsifying Drug Delivery System (SEDDS) Based on VESIsorb® Formulation Technology Improving the Oral Bioavailability of Cannabidiol in Healthy Subjects.

Cannabidiol (CBD), a phytocannabinoid compound of Cannabis sativa, shows limited oral bioavailability due to its lipophilicity and extensive first-pass metabolism. CBD is also known for its high intra- and inter-subject absorption variability in humans. To overcome these limitations a novel self-emulsifying drug delivery system (SEDDS) based on VESIsorb® formulation technology incorporating CBD, as Hemp-Extract, was developed (SEDDS-CBD). The study objective was to evaluate the pharmacokinetic profile of SEDDS-CBD in a randomized, double-blind, cross-over design in 16 healthy volunteers under fasted conditions. As reference formulation, the same Hemp-Extract diluted with medium-chain triglycerides (MCT-CBD) was used. CBD dose was standardized to 25 mg. Pharmacokinetic parameters were analyzed from individual concentration-time curves. Single oral administration of SEDDS-CBD led to a 4.4-fold higher Cmax and a 2.85-/1.70-fold higher AUC0-8h/AUC0-24h compared to the reference formulation. Tmax was substantially shorter for SEDDS-CBD (1.0 h) compared to MCT-CBD (3.0 h). Subgroup analysis demonstrated a higher bioavailability in women compared to men. This difference was seen for MCT-CBD while SEDDS-CBD mitigated this gender effect. Overall, SEDDS-CBD showed a significant improvement for all determined pharmacokinetic parameters: increased CBD plasma values (Cmax), favorably enhanced bioavailability (AUC) and fast absorption (Tmax). No safety concerns were noted following either administration.