Mucoadhesive Buccal Film of Estradiol for Hormonal Replacement Therapy: Development and In-Vivo Performance Prediction

Abstract

The age-related loss of circulating estrogen that occurs during the menopausal transition manifests itself through a variety of symptoms including vasomotor (hot flushes and night sweats), genito-urinary syndrome (vaginal dryness and urinary symptoms), sexual dysfunction, mood, and sleep disturbance that often last longer than a decade. Furthermore, reductions in estrogen level increase the risks of chronic complications such as osteoporosis, cardiovascular disease, and cognitive decline among others, thereby affecting the quality of life of women. Although oral estrogens are the most widely used therapy for menopausal symptoms, they suffer from poor bioavailability, and there are concerns over their safety, creating a significant concern to consumers. Mucoadhesive buccal films are an innovative dosage form that offers several advantages including avoidance of the first-pass metabolism, fast onset of action, and importantly, improved patient acceptance. In the current work, we developed mucoadhesive estradiol film for hormonal replacement therapy using film-forming polymers. Two approaches, namely, co-solvency and nano-emulsion were evaluated to increase solubility and hence incorporate estradiol, a poorly water-soluble drug, into a formulation made from the hydrophilic polymer/s. The films were characterised for their mechanical and physicochemical properties. In-vitro release study showed that about 80% of the drug was released within 6 min from films prepared by the nano-emulsion approach, whereas it took about 10.5 min to get similar drug release from films prepared by the co-solvency approach. The ex-vivo permeation result indicates that about 15% of the drug permeated across the porcine buccal mucosa in the first 10 h from films prepared by the nano-emulsion approach, while permeation across porcine buccal mucosa was only observed at around 24 h from films prepared by the co-solvency method. The nano-emulsion films were evaluated for in vivo performance using a convolution technique using R software. The predicted Cmax and Tmax were found to be 740.74 ng mL−1 and 7 min, respectively, which were higher than previously reported in vivo concentration from oral tablets. The results demonstrated that mucoadhesive film of estradiol based on the nano-emulsion approach could be a promising platform for the delivery of estradiol through the buccal mucosa for the treatment of menopausal symptoms.

In Vitro and In Vivo Characterisation of a Mucoadhesive Buccal Film Loaded with Doxycycline Hyclate for Topical Application in Periodontitis

“…The studied films presented tensile stress values in the range of 0.122 ± 0.012–0.39 ± 0.066 MPa ( Table 3 ), a lower value being observed at F2. The values obtained are comparable to those obtained in previous studies [ 37 ] and the differences between the three formulations were statistically significant (F1/F2, F1/F3, F2/F3, p < 0.001).…”

“…The pH measurement provided information on the tolerance of the films, because acidic or basic pH can be irritating to the mucosa. The studied film samples presented values between 5.9 ± 0.20 and 6.8 ± 0.27 ( Table 3 ), a pH range of 5.5–7.0 being considered well tolerated [ 37 ].…”

“…To understand the mechanism of Doxy Hyc release, correlation coefficients (R 2 ) and release rate constants (K) for various models (zero order, first order, Higuchi and Korsemeyer–Peppas model) [ 37 ] were determined for all studied film batches by Microsoft Excel.…”

Development and Optimization of Imiquimod-Loaded Nanostructured Lipid Carriers Using a Hybrid Design of Experiments Approach

“… 62 As shown in Figure 10 , such a release pattern could be regarded as potentially advantageous for topical application as it can help to initiate a high drug concentration gradient to increase the diffusion force for drug permeation through the stratum corneum. 17 , 63 It has also been reported in the literature that the release mechanism of other formulations including NLCs containing curcumin 64 and estradiol-loaded polymeric films 65 was also best described using the Hopfenberg model.…”

Harnessing the Synergistic Potential of 3D Printed Buccal Films and Nanostructured Lipid Carriers (NLCs) For Personalised Cannabidiol Delivery

“…The method used to determine the in vitro release of CBD from the buccal lm was similar to the one reported by our research group earlier 53 . The lm was placed in a Falcon tube with 10 mL of simulated salivary uid (SSF) and kept in a shaking water bath (Julabo SW22, Germany) at 37 ± 0.5 °C while being stirred at 50 rpm.…”