Background: This study aimed to evaluate the efficacy and safety of oral hydrolyzed collagen peptide (HCP) in healthy females by assessing the skin parameters via biophysical and skin imaging techniques. Methods: 112 females were randomly assigned to receive either HCP (n = 57; 10 g CollaSel Pro^®) or placebo (n = 55; 10 g maltodextrin) daily for eight weeks. The contribution of HCP to skin elasticity, hydration, and roughness was investigated against a placebo, while the facial soft tissue sagging (RMS) and safety data were also recorded. Results: HCP was associated with significant improvements in skin elasticity (p = 0.009), skin hydration (p ranged from 0.003 to <0.001), and skin roughness (p ranged from 0.002 to <0.001). In the HCP vs. the placebo group, week eight values for skin elasticity (43.0 (7.4) vs. 40.3 (3.3) mPa, p = 0.017), skin hydration (65.8 (18.9) vs. 53.1 (14.9) g/m³, p < 0.001) and skin roughness (40.2 (20.4) vs. 24.9 (20.9) g/m³, p < 0.001) were significantly higher. In the HCP group, week 8 RMS values were significantly lower than baseline values (1.02 (0.21) vs. 1.10 (0.21) mm, p = 0.012). Conclusions: CollaSel Pro^® HCP can be considered a well-tolerated, safe product that effectively improves dermal health and the appearance of sagging and ameliorates the signs of the aging process.

To define the bioequivalence (BE) of two orally administered film coated tablets containing 40 mg lurasidone hydrochloride. A single-dose, open-label, randomized two-way crossover trial was conducted under fed conditions, with a washout period of at least one week. Blood samples were drawn over a period of 72 h and plasma concentrations were analysed using a Liquid Chromatography tandem Mass Spectrometry (LC–MS/MS) method. The Pharmacokinetic (PK) parameters were calculated using Phoenix WinNonlin software, based on non-compartmental analysis. The two one-sided hypothesis at the α = 0.05 level of significance was tested by constructing the 90% confidence interval of two one-sided t-tests for the geometric mean ratios test versus reference preparation with analysis of variance (ANOVA). After oral administration of 40 mg lurasidone hydrochloride under fed conditions, the mean area under the curve (AUC_t, AUC_∞) and maximum plasma concentrations (C_max) were 175 ng/mL*h; 184 ng/mL*h and 60 ng/mL, respectively for the test product and 185 ng/mL*h; 198 ng/mL*h and 59 ng/mL respectively for the reference product. 90% Confidence Intervals (CI) for all PK parameters were within the acceptance range of 80.00–125.00%. BE was demonstrated between the generic product and the innovator product in healthy Caucasian male subjects. No clinically meaningful differences in safety or tolerability were observed.

Background: This study aimed to compare the pharmacokinetics and relative bioavailability of two novel cannabidiol (CBD) formulations including bioavailability-enhanced capsule (CBDNEXT Supra capsule) and a bioavailability-enhanced liquid (CBDNEXT Supra liquid)– against a standard high-purity CBD isolate capsule in healthy volunteers under fed (low-fat) conditions. Methods: A single-dose, open-label, randomized, three-period, three-sequence crossover trial was conducted in 12 healthy male volunteers (18–50 years). Of the 12 enrolled subjects, 9 completed all three treatment periods per protocol. Each received 40 mg of CBD as one of three formulations: Test-1 (enhanced CBD capsule), Test-2 (enhanced CBD liquid), or Reference (unformulated CBD isolate capsule with microcrystalline cellulose only as excipient), with a washout of 14 days between treatments. All doses were administered 30 min after a standardized low-fat (~ 300–350 kcal, < 10 g fat) breakfast to minimize the impact of dietary fat on CBD absorption. Blood samples were collected up to 72 h post-dose for plasma CBD and 7-hydroxy-CBD analysis by a validated LC–MS/MS method (LLOQ 0.1 ng/mL). Pharmacokinetic (PK) parameters (C_max, tmax, AUC_0–72, and t_1/2) were determined by non-compartmental analysis. Safety was assessed by adverse events (AEs), vital signs, and laboratory tests (including liver enzymes). Plasma cortisol was measured pre-dose and at 2-, 4-, and 8-hours post-dose as an exploratory pharmacodynamic marker. Results: Nine subjects completed all treatments (three withdrew: two for positive drug screens and one for an intercurrent moderate infection). Mean plasma CBD concentration–time profiles for the three formulations demonstrated markedly different absorption kinetics. The enhanced capsule achieved the highest peak CBD concentration (C_max 14.1 ng/mL) and exposure (AUC_0–72 38.0 h·ng/mL), compared to the enhanced liquid (C_max 6.2 ng/mL, AUC_0–72 20.2 h·ng/mL) and the reference capsule (C_max 2.4 ng/mL, AUC_0–72 11.7 h·ng/mL). The time to peak concentration (tmax) was shortest for the liquid (median ~ 1.0 h), followed by the capsule (2.0 h), and longest for the reference (6.0 h). Inter-individual variability in C_max and AUC was substantially lower for both novel formulations (coefficients of variation ~ 27–44%) than for the reference (> 90%). Statistical analysis confirmed that both the enhanced capsule and liquid produced significantly greater C_max and AUC_0–72 than the reference (geometric mean C_max ratios ~ 566% and ~ 248%, AUC_0–72 ratios ~ 328% and ~ 166%, respectively; 90% confidence intervals did not include 100%). The 7-hydroxy-CBD metabolite reached much lower plasma levels than parent CBD for all treatments (C_max 0.4–1.8 ng/mL, ~ 5–13% of parent C_max), with a slightly delayed tmax (~ 2–6 h) and similar elimination half-life. No serious AEs occurred. The only treatment-related AE was mild-to-moderate transient headache in four subjects (1 on capsule, 2 on liquid, 1 on reference), all resolved without intervention. No clinically significant changes in liver function tests or other laboratory values were observed. Plasma cortisol levels remained within normal ranges after all treatments, with a decline over 8 h consistent with the normal diurnal rhythm and no significant differences between formulations. Conclusions: Both novel formulations markedly improved CBD oral bioavailability under low-fat fed conditions relative to an unformulated CBD isolate capsule. The enhanced capsule in particular achieved a ~ 5.7-fold higher C_max and ~ 3.3-fold higher AUC than the reference, while the enhanced liquid was absorbed ~ 2.5-fold faster. Variability was reduced with the new formulations, and both were well tolerated at the 40 mg dose. These results indicate that the surfactant/acid formulation technology effectively enhances CBD absorption even with a low-fat meal, potentially obviating the need for high-fat co-administration. Further clinical studies (including in female subjects and at steady state) are warranted to confirm these pharmacokinetic advantages in broader populations. Trial registration: Not prospectively registered (pilot pharmacokinetic study without therapeutic intent, thus not subject to mandatory registration).

Objectives: This study aims to evaluate the efficacy and safety of oral supplementation with hydrolyzed collagen peptides (HCP) type I and type III (CollaSel PRO^®) in reducing joint pain and stiffness and improving physical function in patients with osteoarthritis (OA). Methods: In this randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov Identifier: NCT05369780; approved by the Institutional Review Board), 160 adult patients with OA (mean age 52.4 ± 4.3 years; 111 females, 49 males) were randomly assigned to receive either 10 g/day of CollaSel PRO^® (n = 80) or placebo (maltodextrin, n = 80) for 8 weeks. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used to evaluate knee and hip joints, and the American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale (AOFAS-AHFS) was used for ankle joints. Assessments were conducted at baseline and at weeks 1, 4, and 8. Results: In the CollaSel PRO^® group, a significant decrease in WOMAC scores (mean ± SD 50.5 ± 17.0, 40.7 ± 16.9 and 33.8 ± 16.5 vs. 53.7 ± 16.9, respectively, p < 0.001 for each) and significant increase in AOFAS-AHFS scores (64.2 ± 13.1, 73.6 ± 12.3 and 80.8 ± 9.9 vs. 61.8 ± 13.9, respectively, p < 0.001 for each) were noted at weeks 1, 4, and 8 compared to the baseline scores. WOMAC scores were significantly lower in comparing HCP and placebo, and AOFAS-AHFS scores were higher in the HCP group compared to the placebo group at weeks 4 and 8 (all p < 0.001). Conclusions: CollaSel PRO^® appears to be a safe and effective option for the symptomatic management of osteoarthritis. It significantly improved joint pain, stiffness, and physical function in multiple joints. These improvements are not only statistically significant but also clinically meaningful, supporting the need for longer-term evaluation.

The study was designed to evaluate the bioavailability of two rofecoxib (CAS 162011-90-7) tablet formulations. Twenty-four healthy male volunteers were administered a 25 mg tablet of the test formulation (Ecrox®) containing rofecoxib or the originator product (reference). The trial was performed according to an open, cross-over design with a wash-out period of 7 days. Blood samples were taken up to 72 h post dose, the plasma was separated and the concentrations of rofecoxib were determined by an HPLC method. The mean C_max were 192.07 ng/mL and 187.35 ng/mL, while the mean AUC_0–t were 3613.84 ng · h/mL and 3501.56 ng · h/mL for the test and reference formulations, respectively. The median t_max was 3.75 h for the test tablet and 4.00 h for the reference formulation. The mean t_{1/2 el} was 10.66 h and 10.61 h for the test and reference formulation, respectively. Mean MRT values for the test and reference tablets were 15.34 h and 15.33 h, respectively. No significant differences of pharmacokinetic parameters between the two studied formulations were found. The 90 % confidence interval for the primary target parameters, i.e. intra-individual ratios of AUC_0–t and C_max of rofecoxib were between 0.99 and 1.10 (AUC_0–t) as well as between 0.96 and 1.10 (C_max) and thus within the acceptance ranges. Concerning the secondary parameter t_max the 90 % confidence interval for the intra-individual differences was between -0.25 and 0.25 h. In the light of the present study it can be concluded that the two evaluated rofecoxib formulations, i.e. test tablets of rofecoxib and a reference preparation are bioequivalent in terms of the rate and extent of absorption. Studie zur Bioäquivalenz von Rofecoxib-Tabletten An 24 gesunden Probanden, die 25 mg einer Rofecoxib (CAS 162011-90-7)-Testzubereitung (Ecrox®) oder das Originalprodukt erhielten, wurde eine Bioäquivalenzstudie als offene Crossover-Studie mit einer Wash-out-Phase von 7-14 Tagen durchgeführt. Blutentnahmen erfolgten bis zu 72 h nach der Gabe. Die Bestimmung der Rofecoxib-Konzentratio-nen im Plasma wurde mittels HPLC vorgenommen. Die Mittelwerte betrugen für C_max192,07 ng/ml (Test) bzw. 187,35 ng/ml (Referenz), für die AUC_0–inf 3767,40 ng × h/ml (Test) und 3640,44 ng × h/ml (Referenz). Für t_max wurde ein Median von 3,75 h bzw. 4,00 h für die Test- bzw. Referenzzubereitung berechnet. Die mittlere t_1/2 betrug entsprechend 10,66 h bzw. 10,61 h. Die durchschnittliche MRT (mean residence time) für Test bzw. Referenz betrug 15,34 h bzw. 15,33 h. Signifikante Unterschiede wurden hinsichtlich der pharmakokinetischen Parameter zwischen beiden Formulierungen nicht gefunden. Die 90 %-Konfidenzintervalle der primären Zielparameter, der intraindividuellen Quotienten (Test vs. Referenz) von AUC_0–inf und C_max, lagen zwischen 0,99 und 1,09 (AUC_0–inf) und 0,96 und 1,10 (C_max) und somit innerhalb der Akzeptanzgrenzen. Für den sekundären Zielparameter t_max lag das 90%-Konfidenzin-tervall der intraindividuellen Differenz (Test minus Referenz) zwischen -0,25 und 0,25 h. Für die beiden untersuchten Rofecoxib-Zubereitungen kann hinsichtlich Geschwindigkeit und Grad der Resorption Bioäquivalenz angenommen werden. Rofekoksib aktif maddesi içeren iki tablet formülasyonu ile yapilan in vivo biyoeşdeğerlik çalışması Bu klinik çalışma rofekoksib (CAS 162011-90-7) içeren iki tablet formülasyo-nunun karşılaştırılması amacıyla 24 sağlıklı erkek gönüllü ile yapılmıştır. Çalışma her gönüllüye aç karnına, bir seferde 1 adet 25 mg rofekoksib tablet verilerek (tek doz); açık,tek merkezli, randomize, çapraz tasarımlı ve arasında 7 günlük temizlenme dönemi olacak şekilde iki periyodlu olarak gerçekleştirilmiştir. Kan örnekleri ilaç uygulamasını takiben 72 saat içinde alınmış, plazmaları ayrılmış ve rofekoksib konsantrasyonları HPLC yöntemi ile ölçülmüştür. Rofekoksib’ in ortalama C_max değerleri test ve referans tabletler için sırasıyla 192.07 ng/mL ve 187.35 ng/mL, iken, ortalama AUC_0–t değerleri sırasıyla 3613.84 ng · h/mL ve 3501.56 ng · h/mL olarak bulundu. Median t_max, test ve referans üründe sırasıyla 3.75 saat ve 4.00 saat idi. Ortalama t_1/2, test formülasyonu için 10.66 saat ve referans formülasyon için 10.61 saat idi. Araştırılan iki ürünün farmakokinetik parametreleri arasında anlamlı farklar saptanmadı. Rofekoksib’ in birincil hedef parametrelerindeki birey içi oranlarının % 90 güven aralığı, AUC_0–t için 0.99-1.10 arasında ve C_max için 0.96-1.10 arasında olduğundan, kabul edilebilir sınırlar da-hilindeydi. İkincil parametre olan t_max’in birey içi farklarınin % 90 Güven aralığı, -0.25 ve 0.25 arasındaydı. Mevcut çalışmanın ışığında, değerlendirilen iki rofekoksib tablet formülasyonunun (test ve referans) emilim hızı ve kana geçen miktar anlamında biyoeşdeğer oldukları sonucuna varıldı.