Development and optimization of raloxifene hydrochloride loaded lipid nanocapsule based hydrogel for transdermal delivery
Development and optimization of raloxifene hydrochloride loaded lipid nanocapsule hydrogel for transdermal delivery.
A 33 Box-Behnken Design and numerical optimization was performed to obtain the optimized formulation. Subsequently, the optimized raloxifene hydrochloride loaded lipid nanocapsule was developed using phase inversion temperature and characterized for physicochemical properties. Furthermore, the optimized lipid nanocapsule was loaded into a hydrogel and evaluated for rheology, spreadability, ex-vivo skin permeation, deposition and irritation.
The numerical optimization suggested an optimal formula with desirability value of 0.852 and low prediction errors. The optimized formulation showed good % drug entrapment efficiency (79.56 ± 2.34%), nanometer size (56.68 ± 1.2 nm), monodisperse nature (PDI = 0.176 ± 0.2), spherical morphology and good drug-excipient compatibility. The raloxifene hydrochloride loaded lipid nanocapsule hydrogel showed shear thinning properties, sustained drug delivery, dermal compatibility and significantly higher permeability (2-fold), retention (3.37) for raloxifene hydrochloride compared to the control.
The present study showed a successful development of raloxifene hydrochloride loaded lipid nanocapsule hydrogel with improved skin permeation, retention, and good topical compatibility. This formulation may overcome the challenges associated with raloxifene hydrochloride oral delivery including low bioavailability.
Raloxifene hydrochloride is used for the treatment of osteoporosis in women who have undergone menopause. It is available in market as a tablet. However, currently available tablets are only able to deliver a small quantity of the drug into the parts of the body where it is needed, reducing the effects of the medication. This occurs due to the low solubility of Raloxifene hydrochloride in the water and extensive metabolism by the liver before reaching to the systemic circulation. The authors in this study prepared a new gel for skin application. They anticipated that the drug from this gel would slowly and efficiently reach to the site of action from the skin. This will reduce the incidences of unwanted effects and improve the condition of osteoporosis in postmenopausal women. The authors evaluated the drug release behavior, skin absorption, deposition, and safety of the developed gel in rats. They found that the prepared gel slowly and efficiently releases the drug across the skin with no signs of irritation.
