Topical Magnesium Orotate Lipogel in Kidney Transplant Recipients with Persistent Hypomagnesemia: Formulation Development and Pilot Clinical Study.

Background: In solid-organ transplant recipients, hypomagnesemia is a frequent and persistent complication, predominantly related to long-term use of calcineurin inhibitors. Oral magnesium supplementation is often ineffective due to poor adherence, gastrointestinal adverse effects, and high treatment costs. Objectives: This pilot study aimed to (i) develop a topical magnesium formulation for use in renal transplant recipients with persistent hypomagnesemia; (ii) evaluate the influence of formulation excipients on magnesium release from pharmaceutical preparations; and (iii) preliminarily assess the clinical outcomes, functional parameters, patient satisfaction, and tolerability associated with topical magnesium lipogel use in renal transplant recipients with persistent hypomagnesemia. Materials and Methods: Three lipogel formulations containing magnesium orotate, citrate, or sulfate were prepared and characterized in terms of organoleptic properties, pH, colloidal stability, and rheological behavior. In vitro magnesium release was evaluated using Franz diffusion cells. The formulation demonstrating the most favorable release profile, magnesium orotate lipogel, was administered twice daily for two months to 21 renal transplant recipients with persistent hypomagnesemia who had shown inadequate response, intolerance, or non-adherence to oral magnesium supplementation. Laboratory parameters were assessed at baseline and after treatment. Patient satisfaction was evaluated using the Lübeck questionnaire, while physical activity and exercise capacity were assessed using the International Physical Activity Questionnaire (IPAQ) and metabolic equivalent task (MET) calculations. Results: Franz cell studies demonstrated superior magnesium release from the magnesium orotate lipogel compared with the other formulations. After two months, serum magnesium levels were higher than baseline (1.554 ± 0.124 vs. 1.448 ± 0.111 mg/dL, p < 0.001), although they remained below the normal reference range. No significant changes were observed in eGFR or hsCRP. Moderate-intensity physical activity increased significantly (310.475 ± 92.505 vs. 279.286 ± 89.907 MET-min/week, p < 0.001), while vigorous-intensity activity did not change significantly. No relevant adverse effects were reported. Patient satisfaction was high across all evaluated domains, including practicability (86.6%), efficacy (96.4%), tolerability (97.1%), and trust in medical professionals (97.6%). Conclusions: In this pilot study, topical magnesium orotate lipogel was well tolerated and accepted by renal transplant recipients with persistent hypomagnesemia. Serum magnesium levels and moderate physical activity improved over the two-month observation period, although magnesium levels remained below the normal range. These preliminary findings warrant confirmation in larger, randomized, placebo-controlled studies.