Preparation, Optimization, and Evaluation of Hyaluronic Acid-Based Hydrogel Loaded with Miconazole Self-Nanoemulsion for the Treatment of Oral Thrush.

Miconazole nitrate (MZ) is a BCS class II antifungal poorly water-soluble drug with limited dissolution properties and gastrointestinal side effects. Self-nanoemulsifying delivery system-based gel of MZ can improve both solubility and oral mucosal absorption with enhanced antifungal activity. The study aims to formulate MZ self-nanoemulsion (MZ-NE) and combine it within hyaluronic acid-based gel. MZ solubility in various oils, surfactants, and cosurfactant used in NE formulations were evaluated. Mixture design was implemented to optimize the levels of NE components as a formulation variable to study their effects on the mean globule size and antifungal inhibition zones. Further, the optimized MZ-NE was loaded into a hyaluronic acid gel base. Rheological behavior of the prepared gel was assessed. Ex vivo permeability of optimized formulation across buccal mucous of sheep and inhibition against Candida albicans were examined. Mixture design was used to optimize the composition of MZ-NE formulation as 22, 67, and 10% for clove oil, Labrasol, and propylene glycol, respectively. The optimized formulation indicated globule size of 113 nm with 29 mm inhibition zone. Pseudoplastic flow with thixotropic behavior was observed, which is desirable for oral gels. The optimized formulation exhibited higher ex vivo skin permeability and enhanced antifungal activity by 1.85 and 2.179, respectively, compared to MZ-SNEDDS, and by 1.52 and 1.72 folds, respectively, compared to marketed gel. Optimized MZ-NE hyaluronic acid-based oral gel demonstrated better antifungal activity, indicating its potential in oral thrush pharmacotherapy.

Oral gel loaded with penciclovir-lavender oil nanoemulsion to enhance bioavailability and alleviate pain associated with herpes labialis.

Herpes labialis, caused by herpes simplex virus type 1, is usually characterized by painful skin or mucosal lesions. Penciclovir (PV) tablets are found to be effective against herpes labialis but suffer from poor oral bioavailability. This study aimed to combine the benefits of PV and lavender oil (LO), which exhibits anesthetic activity, in the form of a self-nanoemulsifying drug delivery system (SNEDDS) for the treatment of herpes labialis. Toward this purpose, LO (oil), Labrasol:Labrafil M1944 CS in the ratio of 6:4 (surfactant mixture), and Lauroglycol-FCC (co-surfactant, selected based on the solubility of PV) were evaluated as the independent factors using a distance quadratic mixture design. The formulation was optimized for the minimum globule size and maximum stability index and was determined to contain 14% LO, 40.5% Labrasol:Labrafil 1944 (6:4), and 45.5% Lauroglycol-FCC. The optimized PV-LO-SNEDDS was embedded in chitosan hydrogel and the resulting formulations coded by (O3) were prepared and evaluated. The rheological studies demonstrated a combined pseudoplastic and thixotropic behavior with the highest flux of PV permeation across sheep buccal mucosa. Compared to a marketed 1% PV cream, the O3 formulation exhibited a significantly higher and sustained PV release, nearly twice the PV permeability, and a relative bioavailability of 180%. Overall, results confirm that the O3 formulation can provide an efficient delivery system for PV to reach oral mucosa and subsequent prolonged PV release. Thus, the PV-LO-SNEDDS embedded oral gel is promising and can be further evaluated in clinical settings to establish its therapeutic use in herpes labialis.

Physically Optimized Nano-Lipid Carriers Augment Raloxifene and Vitamin D Oral Bioavailability in Healthy Humans for Management of Osteoporosis.

Raloxifene hydrochloride (RLX) is a selective estrogen receptor modulator and Vitamin D (Vit.D) is an important fat-soluble vitamin usually administrated concurrently to treat postmenopausal osteoporosis. Both drugs have low bioavailability due to absorption problems associated with low solubility. The aim of this research was to combine the 2 drugs in nanostructure lipid carriers (NLCs) in order to overcome the previously mentioned drawbacks. Face centered central composite design combined with relative weight-based desirability index was used to optimize RLX-Vit.D-NLCs and investigate the effect of independent variables on NLCs size, entrapment, dissolution, and permeation efficiencies. Pharmacokinetic parameters of optimized NLCs were tested in healthy human volunteers. The results showed that NLCs obtained at 9.37:1 lipid/drug ratio, 1.35:4 Sefsol 218/Glyceryl monostearate ratio and 2.25% Cremophor were 98 nm bearing 82.7% and 57.3% of RLX, and Vit.D, respectively. These nanocarriers enhanced RLX bioavailability by 385.6% relative to commercial product. The level of Vit.D metabolite was significantly increased from an average baseline level of 91 ± 29 nmol/L to 174 ± 36 nmol/L. High level correlation was found between fractions of RLX absorbed and dissolved. Significant improvement of RLX and Vit.D bioavailability through encapsulation within NLCs encourages its use in the treatment of postmenopausal osteoporosis compared to commercialized products.