Design and physicochemical characterization of spray-dried microcapsules encapsulating o/w emulsion-based drug...

Sarcopenia is closely associated with deficiencies in key bioactive compounds, including omega-3 (O3), coenzyme Q10 (CoQ10), vitamin D3 (D3), and L-leucine (Leu). However, the simultaneous oral delivery of these four compounds is challenged by their markedly different physicochemical properties and huge dosage difference. O3 is in the oil state, and Leu has high water solubility, whereas CoQ10 and D3 exhibit very low water solubility. Furthermore, the large total dose and differences in therapeutic doses limit the bioavailability and development of oral formulations. Spray-dried microcapsules encapsulating oil-in-water (o/w) emulsions by dispersing CoQ10 and D3 in O3, while Leu and gelatin were added in maltodextrin-added deionized water for the simultaneous co-delivery of four drugs. Five emulsifiers-such as poloxamer 188, poloxamer 407, sodium caseinate, lecithin, and glycerol monostearate-and the concentration of gelatin (125, 250, or 375 mg) were varied to optimize the formulations. Among seven formulations (F1-F7), the spray-dried microcapsule (F2) containing poloxamer 407 and 250 mg gelatin (1%) achieved the highest encapsulation efficiency for all three actives (CoQ10: 97.14 ± 1.39%, D3: 83.85 ± 3.18%, Leu: 96.07 ± 0.90%) and demonstrated the most favorable powder properties and flowability. F7, which had a high concentration of gelatin (375 mg), exhibited irregular and non-free-flowing powder properties. Instrumental analysis confirmed that CoQ10 and D3 in F2 were successfully converted from their crystalline forms to an amorphous state in spray-dried microcapsules, while the intrinsic peaks of the functional groups of all the drugs were retained. F2 and F7 exhibited the highest dissolution of poorly water-soluble CoQ10 (∼71-72%) and D3 (∼74%) at 60 min in pH 6.8 phosphate buffer containing 0.5% sodium dodecyl sulfate. Highly water-soluble Leu was completely released in all formulations within 60 min, with a slight initial delay attributed to the physical barrier effect of the oil phase and the gelatin wall material. Optimal F2 also showed good short-term stability at 25 °C room temperature for 1 month, confirming negligible changes in both drug content and dissolution profiles. The current spray-dried microcapsules encapsulating o/w emulsion-based drug combinations provide a promising and versatile platform for the simultaneous encapsulation and oral delivery of multiple bioactive compounds with diverse physicochemical properties.