Formulation Development and Evaluation of Cannabidiol Hot-Melt Extruded Solid Self-Emulsifying Drug Delivery System for Oral Applications.

Cannabidiol (CBD) is a highly lipophilic compound with poor oral bioavailability, due to poor aqueous solubility and extensive pre-systemic metabolism. The aim of this study was to explore the potential of employing Hot Melt Extrusion (HME) technology for the continuous production of Self Emulsifying Drug Delivery Systems (SEDDS) to improve the solubility and in vitro dissolution performance of CBD. Accordingly, different placebos were processed through HME in order to obtain a lead CBD loaded solid SEDDS. Two SEDDS were prepared with sesame oil, Poloxamer 188, Gelucire®59/14, PEO N80 and Soluplus®. Moreover, Vitamin E was added as an antioxidant. The SEDDS formulations demonstrated emulsification times of 9.19 and 9.30 min for F1 and F2 respectively. The formed emulsions showed smaller droplet size ranging from 150-400 nm that could improve lymphatic uptake of CBD and reduce first pass metabolism. Both formulations showed significantly faster in vitro dissolution rate (90% for F1 and 83% for F2) compared to 14% for the pure CBD within the first hour, giving an enhanced release profile. The formulations were tested for stability over a 60-day time period at 4°C, 25°C, and 40°C. Formulation F1 was stable over the 60-day time-period at 4°C. Therefore, the continuous HME technology could replace conventional methods for processing SEDDS and improve the oral delivery of CBD for better therapeutic outcomes.

Quality by design approach for fabrication of extended-release buccal films for xerostomia employing hot-melt extrusion technology.

The study endeavors the fabrication of extended-release adipic acid (APA) buccal films employing a quality by design (QbD) approach. The films intended for the treatment of xerostomia were developed utilizing hot-melt extrusion technology. The patient-centered quality target product profile was created, and the critical quality attributes were identified accordingly. Three early-stage formulation development trials, complemented by risk assessment aligned the formulation and process parameters with the product quality standards. Employing a D-optimal mixture design, the formulations were systematically optimized by evaluating three formulation variables: amount of the release-controlling polymer Eudragit® (E RSPO), bioadhesive agent Carbopol® (CBP 971P), and pore forming agent polyethylene glycol (PEG 1500) as independent variables, and % APA release in 1, 4 and 8 h as responses. Using design of experiment software (Design-Expert®), a total of 16 experimental runs were computed and extruded using a Thermofisher ScientificTM twin screw extruder. All films exhibited acceptable content uniformity and extended-release profiles with the potential for releasing APA for at least 8 h. Films containing 30% E RSPO, 10% CBP 971P, and 20% PEG 1500 released 88.6% APA in 8 h. Increasing the CBP concentration enhanced adhesiveness and swelling capacities while decreasing E RSPO concentration yielded films with higher mechanical strength. The release kinetics fitted well into Higuchi and Krosmeyer-Peppas models indicating a Fickian diffusion release mechanism.

Formulation Development of Solid Self-Nanoemulsifying Drug Delivery Systems of Quetiapine Fumarate via Hot-Melt Extrusion Technology: Optimization Using Central Composite Design.

Quetiapine fumarate (QTF) was approved for the treatment of schizophrenia and acute manic episodes. QTF can also be used as an adjunctive treatment for major depressive disorders. QTF oral bioavailability is limited due to its poor aqueous solubility and pre-systemic metabolism. The objective of the current investigation was the formulation development and manufacturing of solid self-nanoemulsifying drug delivery system (S-SNEDDS) formulation through a single-step continuous hot-melt extrusion (HME) process to address these drawbacks. In this study, Capmul® MCM, Gelucire® 48/16, and propylene glycol were selected as oil, surfactant, and co-surfactant, respectively, for the preparation of S-SNEDDS. Soluplus® and Klucel™ EF (1:1) were selected as the solid carrier. Response surface methodology in the form of central composite design (CCD) was utilized in the current experimental design to develop the S-SNEDDS formulations via a continuous HME technology. The developed formulations were evaluated for self-emulsifying properties, particle size distribution, thermal behavior, crystallinity, morphology, physicochemical incompatibility, accelerated stability, and in vitro drug release studies. The globule size and emulsification time of the optimized SNEDDS formulation was 92.27 ± 3.4 nm and 3.4 ± 3.38 min. The differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) studies revealed the amorphous nature of the drug within the formulation. There were no drug-excipient incompatibilities observed following the Fourier transform infrared (FTIR) spectroscopy. The optimized formulation showed an extended-release profile for 24 h. The optimized formulation was stable for three months (last time-point tested) at 40 °C/75% RH. Therefore, the developed S-SNEDDS formulation could be an effective oral delivery platform for QTF and could lead to better therapeutic outcomes.