Pharmacodynamic Study of Parallel Groups Comparing the Effect of Rivaroxaban 20 Mg (Laboratorios Leti, S.A.V.) vs Rivaroxaban 20 Mg (Bayer Laboratories) on Prothrombin Time

Background: The prevalence of both atrial fibrillation (FA) and diabetes mellitus (DM) is increasing and they often occur together and constitute a high risk of thrombosis. Rivaroxaban is a Factor Xa inhibitor with a rapid onset and disappearance of action after oral administration;it acts by inhibiting the active form of the coagulation factor. In order to reflect the effect of the action of Rivaroxaban, we used the prothrombin time (PT);however, it′s not the most accurate, but it is the one available in our community. Methods: This was a prospective, randomized, analyst-blinded, parallel group clinical study to verify the efficacy of Rivaroxaban Leti 20 mg (RL) (12 volunteers vs Rivaroxaban Bayer 20 mg (RB) (13 volunteers). The variables were determination of PT and Partial Thromboplastin Time (aPTT) at baseline and at 24, 48 and 72 hours after administering a daily dose of 20 mg for three days. The determination was carried out with the IDG method (Integrated Diagnostics Group Sanzay Corporation) with an International Sensitivity Index (ISI) of 1.17 PT and aPTT were taken before the first dose, and then, every day during the next 3 days, three hours after the ingestion of their daily dose at 7 am. Results: The 25 healthy volunteers were similar in age, BMI, and SBP/DBP level with a greater number of men in the Bayer group. The efficacy of rivaroxaban was similar in both groups with prolongation of PTT to the 2nd day of treatment with PT, and percentage changes from baseline (14.46 ± 0.97 for RB vs 14.17 ± 0.94 RL p: 0.45), PTT results and percentage changes from the base (RB: 34 ± 4.53 RL: 33.46 ± 2.82). The safety of rivaroxaban was good in both groups with no serious adverse events. The equivalence in the logarithmically transformed PT result (ln) on day two, Mean and CI (90%) 99.2 (94.4-104) and 100 (99.5-100.8);neither the means nor the 90% confidence intervals of the PT variable transformed logarithmically to ensure its normality, were far from the 80%-125% allowed for declaration of similarity. Conclusion: The test formulation Rivaroxaban Asarap? 20 mg, manufactured by Leti Laboratories, is interchangeable or bioequivalent in clinical and laboratory response to the reference formulation Xarelto? manufactured by Bayer Laboratories.

Double-Blind, Parallel Group Study to Compare the Clinical Effectiveness of Calcium Dobesilate 500 mg BID vs. Calcium Dobesilate LP 1 g OD, in Patients with Chronic Venous Insufficiency of the Lower Limbs

Background: Chronic venous insufficiency (CVI) describes a condition that affects the venous system of the lower extremities due to venous hypertension (VH. The prevalence is between 5% - 30%. CVI is associated with older age, smoking, lower extremity trauma, presence of an arteriovenous shunt, and elevated estrogen levels. All patients should be initially treated with conservative management. Venoactive drugs like calcium dobesilate are useful. Objectives: The primary objective compared the clinical improvement in patients with CVI, grades 0 - 3 of the CEAP classification of chronic venous disease, produced by two formulations of calcium dobesilate: calcium dobesilate LP 1 g OD vs calcium dobesilate 500 mg BID, immediate release. The secondary objective assessed the side effects of both formulations. Method: All patients took one tablet and one capsule at 7 am, and one capsule at 7 pm, for 8 weeks. One group received dobesilate 1 g OD and the other group received dobesilate 500 md BID. They were evaluated after 15, 30 and 60 days of treatment, using the symptom evaluation scale. Results: In both groups, there was a significant decrease in the symptom score after 15 days. Four patients in the Dobesilate OD group: had adverse effects, which did not require suspension of treatment. In the BID dobesilate group, there was one therapeutic failure, and one case of gastric discomfort. Conclusions: Prolonged-release Calcium dobesilate 1 g OD is as effective as calcium dobesilate 500 mg BID for the treatment of patients with chronic venous insufficiency.

Acyclovir-Loaded Solid Lipid Nanoparticles: A Permeation and Penetrability Study

Herpes simplex virus type I is a cutaneous infection treated with acyclovir. The topical treatment has therapeutic challenges due to the deficient delivery of the drug through epithelial barriers. This results in an inadequate drug-virus interaction in the basal epidermis (virus replication site). For this reason, it is essential to generate drug carrier systems that overcome these limitations. In this study, we evaluated the permeation (through in vitro test Franz cells) and penetration (by ex vivo test Tape Stripping) of a topical formulation of acyclovir loaded in solid lipid nanoparticles and a conventional formulation (Aciclor®). The acyclovir solid lipid nanoparticles were prepared using hot homogenization and sonication methods. The results yielded a particle size of 85 ± 2 nm, a polydispersity index of 0.24 ± 0.01, a zeta potential of −16 ± 2 mV, and 94% ± 3% of encapsulated drug. The in vitro test revealed that the permeability of acyclovir solid lipid nanoparticles formulation was superior compared to reference formulation, with values of 1473.74 ± 30.14 µg/cm2 for the solid lipid nanoparticles and 893.36 ± 38.09 µg/cm2 for the reference formulation. The ex vivo test demonstrated that acyclovir solid lipid nanoparticles exhibited superior penetrability through the stratum corneum compared to the reference formulation, with total amounts of 3767 µg for the solid lipid nanoparticles and 2162 µg for the reference formulation. These findings seem promising in advancing new effective therapies against herpes generated by herpes simplex virus type I.

Betamethasone Dipropionate Loaded in Nanoliposomes vs Conventional Betamethasone Dipropionate: Comparative Study of Permeability and Penetrability in Vitro and ex Vivo

A betamethasone dipropionate (BD) liposomal cream was developed to treat rheumatological, inflammatory, allergic diseases and psoriasis. BD is a corticosteroid, anti-inflammatory, and immunosuppressant. However, adverse effects are associated with prolonged topical use. For this reason, liposomes were loaded with BD because they offer excellent biocompatibility, bio adhesiveness, and penetrability that improve the effects caused by the conventional drug. Liposomal dispersions were prepared by emulsification using phospholipid 90 (lipid) and Tween 80 (surfactant). The particle size, polydispersity index (PDI), and zeta potential were measured using a particle analyzer. The betamethasone (BM) percentage of encapsulated active (EA) ingredient was also determined through High Performance Liquid Chromatography (HPLC). The Franz cell and tape stripping characterized these in vitro and ex vivo. Then the final formulation reached a particle size of 70.80 ± 3.31 nm, a PDI of 0.242 ± 0.038, a zeta potential of −11.68 ± 0.77 mv and encapsulate active of 83.1% ± 2.4, complying with the parameters of a nanotechnological formulation. In vitro and ex vivo studies confirmed significantly efficacy of the cream over the commercial product, through the greater penetration into the pig ear skin, resulting in an improved drug. Finally, the liposomal cream demonstrated significant potential for enhanced percutaneous absorption, attributed to its nanometric size. This innovative nanotechnology approach aims to reduce the frequency of topical applications, thereby minimizing the side effects associated with psoriasis treatment.

A Bioequivalence Study of Empagliflozin/Metformin Fixed-Dose Combination in Healthy Subjects under Fasting Conditions

Background: This study evaluated the bioequivalence of empagliflozin 12.5 mg/metformin 1000 mg tablets compared to Synjardy® (Empagliflozin 12.5 mg/metformin 1000 mg) tablets in healthy male subjects under fasting conditions. Methods: This was a phase I, randomized, single-dose, two-period, two-sequence, crossover study to evaluate the bioequivalence (BE) profiles of two fixed-dose combinations (FDCs) of empagliflozin/metformin. Cmax, AUC0-t and AUC0-∞ from test and reference formulations were evaluated to access BE. The plasma concentrations were measured using a validated liquid chromatography-mass spectrometry (LC-MS/MS) method. Of the 24 subjects enrolled, 23 completed both periods of the study. The two formulations test and reference were considered bioequivalent if 90% confidence interval (CI) fell within 80.00% - 125.00% for Cmax, AUC0-t and AUC0-∞. Tolerability and safety were assessed throughout the study. Results: The pharmacokinetic (PK) parameters were similar between the test product (T) and reference product (R) Synjardy®. The 90% CI of the test/reference ratios of log-transformed PK parameters point estimates was Cmax: 89.87% (85.68% - 94.27%), AUC0-t: 87.91% (83.65% - 92.39%) and AUC0-∞: 87.16% (82.80% - 91.75%) to empagliflozin and Cmax: 92.19% (87.95% - 96.65%), AUC0-t: 91.38% (84.42% - 98.91%) and AUC0-∞: 93.78% (83.82% - 104.93%) to metformin respectively (90% CI for all PK parameters fell within 80.00% - 125.00%). Conclusion: Our results demonstrated BE between the test and reference formulations of oral tablets of empagliflozin 12.5 mg/metformin 1000 mg (FDC) in healthy male subjects under fasting conditions.

Randomized, Double-Blind, Double-Masked, Parallel Group Clinical Study to Compare the Effectiveness of Diclofenac Potassium 150 mg, LP OD, vs Diclofenac Potassium 50 mg, TID, Three Times a Day, in Knee Osteoarthritis

Background: Osteoarthritis is a chronic disease associated with pain, inflammation, stiffness and synovial effusion, with progressive functional limitation, compromising quality of life. It progressively leads to loss or decrease in joint function. Pharmacological and non-pharmacological therapy seeks symptomatic management, complicated by a lack of adherence. After acetaminophen, non-steroidal anti-inflammatory drugs such as diclofenac are the most widely used medications. Objectives: The primary objective compared the analgesic effect of diclofenac 150 mg once daily vs. 50 mg three times daily in patients with knee osteoarthritis. The secondary objective assessed changes in quality of life. Method: One group received diclofenac 150 mg OD with placebo TTD. Another group received placebo OD and 50 mg active diclofenac (reference) TTD, both for 30 days. The evaluation of pain was carried out by a visual analog scale (VAS), at the beginning, 2, 3, 4, 15 and 30 days, quality of life (the WOMAC scale) and adverse effects, at 15 and 30 days. Results: Pain decreased significantly on days 15 and 30, compared to day 0, in both groups, without differences between groups. The total results in the WOMAC scale showed a very marked improvement at 15 and 30 days, without differences between groups. The most frequent adverse effects were constipation 6% in the reference group, and gastric discomfort 30.3% in the reference group vs 28.1%, in the Test group. Conclusions: Prolonged-release diclofenac 150 mg OD is as effective as diclofenac 50 mg TID for the treatment of patients with knee osteoarthritis.