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.

Development and Characterization of Different Dosage Forms of Nifedipine/Indomethacin Fixed-Dose Combinations.

Studies have shown that 40 individuals out of 100,000 are diagnosed with rheumatoid arthritis (RA) yearly, with a total of 1.3 million in the United States. Furthermore, the impact of RA in some cases can extend to cardiovascular diseases (CVD), as the studies showed that 84% of RA patients are at risk of developing hypertension. This study aims to design and develop different dosage forms (capsule-in-capsule and three-dimensional (3D) printed tablet) of nifedipine/indomethacin fixed-dose combination (FDC). The hot-melt extrusion (HME) was utilized alone and with fused deposition modeling (FDM) techniques The developed dosage forms were intended to provide delayed-extended and immediate release profiles for indomethacin and nifedipine, respectively. FDC dosage forms were successfully developed and characterized. Nifedipine formulations showed significant improvement in release profiles, having 94% of the drug release at 30 minutes compared with pure nifedipine, which had a percent release of 2%. Furthermore, the release of indomethacin was successfully delayed at a pH of 1.2 and extended at a pH of 6.8. Differential scanning calorimetry results showed endothermic crystalline peaks at 165 °C and 176 °C for indomethacin and nifedipine, respectively. Moreover, the thermal analysis of all formulations showed the absence of the endothermic peaks indicating complete solubilization of indomethacin and nifedipine in the polymeric carriers. All formulations had post-processing drug content in the range of 95% to 98%. Moreover, results from the stability study showed that all formulations were able to remain chemically and physically stable with no signs of recrystallization or degradation. The designed FDC dosage forms could improve the quality of life by enhancing patient compliance and preventing the need for polypharmacy.

Investigation of hot melt extrusion process parameters on solubility and tabletability of atorvastatin calcium in presence of Neusilin® US2.

Reports in the literature indicate that hot-melt extrusion (HME) processing techniques could alter the mechanical properties of the pharmaceutical physical blend, which may alter successful processing during tableting. The aim of this study was to evaluate whether HME processing conditions have an impact on the tabletability of Atorvastatin calcium trihydrate (ATR) in the presence of Neusilin® US2 (NUS2). ATR drug load of 25% was mixed with 75% of NUS2 and extruded using two screw configurations, screw speeds, and feed rates. Solid-state thermal analysis showed that ATR transformed to an amorphous form which led to improved solubility. ATR tabletability was affected positively by screw configuration that had no shearing and mixing force. SEM analysis indicated that a conveying screw configuration preserved the spherical nature of NUS2, thus improving ATR tabletability. This novel study demonstrates the significance of changing and monitoring the HME process parameters, which impact the materials' mechanical properties and may prevent adverse outcomes during tableting.

Recent Advances in the Applications of Additive Manufacturing (3D Printing) in Drug Delivery: A Comprehensive Review.

There has been a tremendous increase in the investigations of three-dimensional (3D) printing for biomedical and pharmaceutical applications, and drug delivery in particular, ever since the US FDA approved the first 3D printed medicine, SPRITAM® (levetiracetam) in 2015. Three-dimensional printing, also known as additive manufacturing, involves various manufacturing techniques like fused-deposition modeling, 3D inkjet, stereolithography, direct powder extrusion, and selective laser sintering, among other 3D printing techniques, which are based on the digitally controlled layer-by-layer deposition of materials to form various geometries of printlets. In contrast to conventional manufacturing methods, 3D printing technologies provide the unique and important opportunity for the fabrication of personalized dosage forms, which is an important aspect in addressing diverse patient medical needs. There is however the need to speed up the use of 3D printing in the biopharmaceutical industry and clinical settings, and this can be made possible through the integration of modern technologies like artificial intelligence, machine learning, and Internet of Things, into additive manufacturing. This will lead to less human involvement and expertise, independent, streamlined, and intelligent production of personalized medicines. Four-dimensional (4D) printing is another important additive manufacturing technique similar to 3D printing, but adds a 4th dimension defined as time, to the printing. This paper aims to give a detailed review of the applications and principles of operation of various 3D printing technologies in drug delivery, and the materials used in 3D printing, and highlight the challenges and opportunities of additive manufacturing, while introducing the concept of 4D printing and its pharmaceutical applications.

Development of Subdermal Implants Using Direct Powder Extrusion 3D Printing and Hot-Melt Extrusion Technologies.

Implants are drug delivery platforms that consist of a drug-polymer matrix with the ability of providing a localized and efficient controlled release of the drug with minimal side effects and achievement of the desired therapeutic outcomes with low drug loadings. Direct powder extrusion (DPE) 3D printing technology involves the extrusion of material through a nozzle of the printer in the form of pellets or powder. The present study aimed at investigating the use of the CELLINK BIO X™ bioprinter using DPE 3D printing technique to fabricate and evaluate the impact of different shapes (cuboid, cylinder, and tube) of raloxifene hydrochloride (RFH)-loaded subdermal implants on the release of RFH from the implants. This study further evaluated the impact of different processing techniques, viz., hot-melt extrusion (HME) technology vs. DPE 3D printing technique, on the release of RFH from the implants fabricated by each processing technique. All the fabricated implants were characterized by XRD, DSC, SEM, and FTIR, and evaluated for their water uptake, mass loss, and in vitro RFH release. The current study successfully demonstrated a great opportunity of controlling and/or tuning the release of RFH from the subdermal implants by altering the implant shape, and hence surface area, and could be a great contribution and/or addition to the personalization of medicines and improvement of patient compliance.

Influence of Poloxamer on the Dissolution and Stability of Hot-Melt Extrusion-Based Amorphous Solid Dispersions Using Design of Experiments.

The current study aimed to see the effects of poloxamer P407 on the dissolution performance of hydroxypropyl methylcellulose acetate succinate (AquaSolve™ HPMC-AS HG)-based amorphous solid dispersions (ASD). A weakly acidic, poorly water-soluble active pharmaceutical ingredient (API), mefenamic acid (MA), was selected as a model drug. Thermal investigations, including thermogravimetry (TG) and differential scanning calorimetry (DSC), were conducted for raw materials and physical mixtures as a part of the pre-formulation studies and later to characterize the extruded filaments. The API was blended with the polymers using a twin shell V-blender for 10 min and then extruded using an 11-mm twin-screw co-rotating extruder. Scanning electron microscopy (SEM) was used to study the morphology of the extruded filaments. Furthermore, Fourier-transform infrared spectroscopy (FT-IR) was performed to check the intermolecular interactions of the components. Finally, to assess the in vitro drug release of the ASDs, dissolution testing was conducted in phosphate buffer (0.1 M, pH 7.4) and hydrochloric acid-potassium chloride (HCl-KCl) buffer (0.1 M, pH 1.2). The DSC studies confirmed the formation of the ASDs, and the drug content of the extruded filaments was observed to be within an acceptable range. Furthermore, the study concluded that the formulations containing poloxamer P407 exhibited a significant increase in dissolution performance compared to the filaments with only HPMC-AS HG (at pH 7.4). In addition, the optimized formulation, F3, was stable for over 3 months when exposed to accelerated stability studies.

Prediction and Construction of Drug-Polymer Binary System Thermodynamic Phase Diagram in Amorphous Solid Dispersions (ASDs).

Amorphous solid dispersion (ASD) has been well known as a potential strategy to improve the bioavailability and dissolution performance of poorly water-soluble drugs. The primary concern of this approach is the long-term stability of the amorphous drug in the solid dispersion. Accurate prediction and detection of the solubility and miscibility of drug in polymeric binary system will be a milestone to the development of ASDs. In this investigation, a method based on Flory-Huggins (F-H) theory was proposed to predict and calculate the solubility and miscibility of the drug in polymeric matrix and construct the phase diagram to identify the relevance between drug loading and temperature for ASDs development. Indomethacin (Indo) was chosen as the model drug, and polyvinyl pyrrolidone vinyl acetate (Kollidon® VA 64) was used as a polymeric carrier for the ASD systems. Physical mixtures were prepared with different drug loadings (10 to 90%) and analyzed by differential scanning calorimetry (DSC). The interaction parameter χ was calculated for physical mixtures by the melting point depression and solubility parameter contribution methods. The phase diagram was constructed to investigate the impact of other parameters like drug loading, processing temperature, and Gibbs free energy of mixing (ΔGmix). For further validation, formulations were developed using HME to verify the accuracy of the phase diagram and to guide in the hot-melt extrusion (HME) process design space and optimization.

CONTINUOUS PRODUCTION OF RALOXIFENE HYDROCHLORIDE LOADED NANOSTRUCTURED LIPID CARRIERS USING HOT-MELT EXTRUSION TECHNOLOGY.

The aim of this study was to utilize a continuous process for the production of orally administered raloxifene hydrochloride (RX-HCl) loaded nanostructured lipid carrier (NLC) formulations for extended drug release using hot-melt extrusion (HME) technology coupled with probe sonication, and also to evaluate the in vitro characteristics of the prepared NLCs. Preparation of the NLCs using HME technology involved two main steps, first formation of a pre-emulsion after extrusion and then size reduction of the pre-emulsion using probe sonication to obtain the NLCs. A screw speed of 100 rpm and a barrel temperature of 85 °C, were used in the extrusion process. NLCs prepared by HME technology showed a lower particle size compared to those prepared by the conventional probe sonication method. The prepared NLCs had high entrapment efficiency values (>90 %). In vitro drug release was evaluated using dialysis bag diffusion technique and USP apparatus I. Overall, the RX-HCl loaded NLCs had a higher rate of drug release than the pure drug. The release profile for the F4-3 NLC formulations and pure drug at the beginning and end of the stability study were comparable. The particle size of the prepared NLCs remained stable over the storage period and all PDI and zeta potential values were ≤ 0.5 and in the range of -15 to -30 mV, respectively, indicating good physical stability of the formulations. In summary, HME technology and probe sonication were successfully used to prepare RX-HCl loaded NLC formulations with shorter processing times as compared to the conventional probe sonication method, which makes this technique a uniquely more industry-friendly method.

Theophylline-nicotinamide pharmaceutical co-crystals generated using hot melt extrusion technology: Impact of polymeric carriers on processability.

The objective of the current study was to develop theophylline (TPH) nicotinamide (NAM) pharmaceutical co-crystals using the hot melt extrusion (HME) technology and evaluate the processability of the co-crystals using different polymeric carriers. A physical mixture of 1:1 M ratio of TPH and NAM was employed to prepare the co-crystals. Hydroxypropylmethylcellulose acetate succinate, polyethylene oxide, and Kollidon® VA-64 (5% w/w) were investigated as polymeric carriers for the HME process. Solid-state characterization using differential scanning calorimetry showed two endothermal peaks, one at 126.4 °C indicating eutectic formation and another at 174 °C indicating the melting point of the co-crystal for all formulations, except the Kollidon® VA-64 extrudates, which showed a single peak at 174 °C. Fourier-transform infrared spectroscopy and powder X-ray diffraction studies revealed the formation of co-crystals. The feasibility to formulate the extrudates into solid dosage forms was assessed by formulating a tablet blend. The three-month stability studies showed no degradation at the accelerated stability conditions of 40 (±2) ° C and 75 (±5) % RH. Finally, the results demonstrated that the presence of mixing zones in screw configuration and extrusion temperature are critical processing parameters that influence co-crystal formation.

A Comparison Between Lab-Scale and Hot-Melt-Extruder-Based Anti-inflammatory Ointment Manufacturing.

Hot-melt extrusion (HME) has been extensively investigated for continuous manufacturing of amorphous solid dispersions, to improve the solubility of poorly water-soluble drug substances, impart abuse deterrence to controlled substances, taste masking for pediatric and geriatric formulations and development of cocrystal system. Much research has been conducted on the continuous manufacturing of solid dosage forms using HME, but its applicability in the manufacturing of semisolids remains an unexplored domain. This study aimed to explore the applicability of HME in the continuous manufacturing of topical semi-solid formulations with two active pharmaceutical ingredients (APIs). Ointments containing a combination of triamcinolone acetonide and lidocaine hydrochloride were screened based on a quality target product profile (QTPP) and established critical quality attributes (CQAs) using design of experiments (DoE). Three selected formulations, manufactured by a lab-scale fusion method and HME, were subjected to further characterization studies including work of adhesion, stiffness, apparent pH, content uniformity, differential scanning calorimetry, accelerated stability, and in vitro drug release testing. Selected formulations met design characteristics and demonstrated the applicability of HME in the continuous manufacturing of semi-solid formulations. Graphical abstract.

Processability of AquaSolve™ LG polymer by hot-melt extrusion: Effects of pressurized CO2 on physicomechanical properties and API stability.

The objective of this study was to investigate the processability of AquaSolve™ hydroxypropyl methylcellulose acetate succinate L grade (HPMCAS LG) via hot-melt extrusion and to examine the effect of pressurized carbon dioxide (P-CO2) on the physicomechanical properties of efavirenz (EFA)-loaded extrudates. To optimize the process parameters and formulations, various physical mixtures of EFA (30%, 40%, and 50%, w/w) and HPMCAS LG (70%, 60%, and 50%, w/w), respectively, were extruded using a co-rotating twin-screw extruder with a standard screw configuration, with P-CO2 injected into zone 8 of the extruder. Thermal characterization of the extrudates was performed using differential scanning calorimetry and thermogravimetric analysis. Scanning electron microscopy was employed to study the morphology and porosity of the formulations. Notably, the macroscopic morphology changed to a foam-like structure by P-CO2 injection resulting in an increased specific surface area, porosity, and dissolution rate. Thus, HPMCAS LG extrusion, coupled with P-CO2 injection, yielded faster dissolving extrudates. Stability studies indicated that HPMCAS LG was able to physically and chemically stabilize the amorphous state of high-dose EFA. Furthermore, the milling efficiency of the extrudates produced with P-CO2 injection improved because of their increased porosity.

Curcumin-loaded Nanostructured Lipid Carriers for Ocular Drug Delivery: Design Optimization and Characterization.

The current study sought to formulate, optimize, and evaluate curcumin-loaded Nanostructured Lipid Carriers (NLCs) for their in vitro and ex vivo characteristics. NLCs, prepared using hot-melt emulsification and ultrasonication techniques, were optimized using a Central Composite Design (CCD) and evaluated for their in vitro physicochemical characteristics. Their stability over a 3 month period and transcorneal permeation across excised rabbit corneas (ex vivo) were assessed for the optimized NLCs. The optimized NLC, with a particle size of 66.8 ± 2 nm, polydispersity index of 0.17±0.05, entrapment efficiency of 96 ± 1.6%, and drug loading of 3.1 ± 0.05% w/w, was chosen using CCD. The optimized NLCs showed optimum ex vivo stability at 4°C for the study period and demonstrated a significant increase in curcumin permeation (~2.5-fold) across the rabbit cornea in comparison to the control. Overall, these studies indicated the successful development of NLCs using the design of experiment approach; the formulation enhanced curcumin permeation across excised corneas and did not show any harmful side effects.

Preparation and evaluation of enteric coated tablets of hot-melt extruded lansoprazole.

The objective of this work was to use hot-melt extrusion (HME) technology to improve the physiochemical properties of lansoprazole (LNS) to prepare stable enteric coated LNS tablets. For the extrusion process, we chose Kollidon® 12 PF (K12) polymeric matrix. Lutrol® F 68 was selected as the plasticizer and magnesium oxide (MgO) as the alkalizer. With or without the alkalizer, LNS at 10% drug load was extruded with K12 and F68. LNS changed to the amorphous phase and showed better release compared to that of the pure crystalline drug. Inclusion of MgO improved LNS extrudability and release and resulted in over 80% drug release in the buffer stage. Hot-melt extruded LNS was physically and chemically stable after 12 months of storage. Both formulations were studied for compatibility with Eudragit® L100-55. The optimized formulation was compressed into a tablet followed by coating process utilizing a pan coater using L100-55 as an enteric coating polymer. In a two-step dissolution study, the release profile of the enteric coated LNS tablets in the acidic stage was less than 10% of the LNS, while that in the buffer stage was more than 80%. Drug content analysis revealed the LNS content to be 97%, indicating the chemical stability of the enteric coated tablet after storage for six months. HME, which has not been previously used for LNS, is a valuable technique to reduce processing time in the manufacture of enteric coated formulations of an acid-sensitive active pharmaceutical ingredient as compared to the existing methods.

Investigation of the combined effect of MgO and PEG on the release profile of mefenamic acid prepared via hot-melt extrusion techniques.

This study aimed to investigate the combined effect of magnesium oxide (MgO) as an alkalizer and polyethylene glycol (PEG) as a plasticizer and wetting agent in the presence of Kollidon® 12 PF and 17 PF polymer carriers on the release profile of mefenamic acid (MA), which was prepared via hot-melt extrusion technique. Various drug loads of MA and various ratios of the polymers, PEG 3350 and MgO were blended using a V-shell blender and extruded using a twin-screw extruder (16-mm Prism EuroLab, ThermoFisher Scientific, Carlsbad, CA) at different screw speeds and temperatures to prepare a solid dispersion system. Differential scanning calorimetry and X-ray diffraction data of the extruded material confirmed that the drug existed in the amorphous form, as evidenced by the absence of corresponding peaks. MgO and PEG altered the micro-environmental pH to be more alkaline (pH 9) and increased the hydrophilicity and dispersibility of the extrudates to enhance MA solubility and release, respectively. The in vitro release study demonstrated an immediate release for 2 h with more than 80% drug release within 45 min in matrices containing MgO and PEG in combination with polyvinylpyrrolidone when compared to the binary mixture, physical mixture and pure drug.

Influence of pressurized carbon dioxide on ketoprofen-incorporated hot-melt extruded low molecular weight hydroxypropylcellulose.

OBJECTIVES: The aim of the current research project was to investigate the effect of pressurized carbon dioxide (P-CO2) on the physico-mechanical properties of ketoprofen (KTP)-incorporated hydroxypropylcellulose (HPC) (Klucel™ ELF, EF, and LF) produced using hot-melt extrusion (HME) techniques and to assess the plasticization effect of P-CO2 on the various polymers tested. METHODS: The physico-mechanical properties of extrudates with and without injection of P-CO2 were examined and compared with extrudates with the addition of 5% liquid plasticizer of propylene glycol (PG). The extrudates were milled and compressed into tablets. Tablet characteristics of the extrudates with and without injection of P-CO2 were evaluated. RESULTS AND CONCLUSION: P-CO2 acted as a plasticizer for tested polymers, which allowed for the reduction in extrusion processing temperature. The microscopic morphology of the extrudates was changed to a foam-like structure due to the expansion of the CO2 at the extrusion die. The foamy extrudates demonstrated enhanced KTP release compared with the extrudates processed without P-CO2 due to the increase of porosity and surface area of those extrudates. Furthermore, the hardness of the tablets prepared by foamy extrudates was increased and the percent friability was decreased. Thus, the good binding properties and compressibility of the extrudates were positively influenced by utilizing P-CO2 processing.

Optimization of hot melt extrusion parameters for sphericity and hardness of polymeric face-cut pellets.

The aim of this study was to formulate face-cut, melt-extruded pellets, and to optimize hot melt process parameters to obtain maximized sphericity and hardness by utilizing Soluplus(®) as a polymeric carrier and carbamazepine (CBZ) as a model drug. Thermal gravimetric analysis (TGA) was used to detect thermal stability of CBZ. The Box-Behnken design for response surface methodology was developed using three factors, processing temperature ( °C), feeding rate (%), and screw speed (rpm), which resulted in 17 experimental runs. The influence of these factors on pellet sphericity and mechanical characteristics was assessed and evaluated for each experimental run. Pellets with optimal sphericity and mechanical properties were chosen for further characterization. This included differential scanning calorimetry, drug release, hardness friability index (HFI), flowability, bulk density, tapped density, Carr's index, and fourier transform infrared radiation (FTIR) spectroscopy. TGA data showed no drug degradation upon heating to 190 °C. Hot melt extrusion processing conditions were found to have a significant effect on the pellet shape and hardness profile. Pellets with maximum sphericity and hardness exhibited no crystalline peak after extrusion. The rate of drug release was affected mainly by pellet size, where smaller pellets released the drug faster. All optimized formulations were found to be of superior hardness and not friable. The flow properties of optimized pellets were excellent with high bulk and tapped density.

Development of multiple structured extended release tablets via hot melt extrusion and dual-nozzle fused deposition modeling 3D printing.

The study aims to fabricate extended release (ER) tablets using a dual-nozzle fused deposition modeling (FDM) three-dimensional (3D) printing technology based on hot melt extrusion (HME), using caffeine as the model compound. Three different ER tablets were developed, which obtained "delayed-release", "rapid-sustained release", and "release-lag-release" properties. Each type of tablet was printed with two different formulations. A novel printing method was employed in this study, which is to push the HME filament from behind with polylactic acid (PLA) to prevent sample damage by gears during the printing process. Powder X-ray diffractometry (PXRD) and differential scanning calorimetry (DSC) results showed that caffeine was predominately amorphous in the final tablets. The dissolution of 3D printed tablets was assessed using a USP-II dissolution apparatus. ER tablets containing PVA dissolved faster than those developed with Kollicoat IR. Overall, this study revealed that ER tablets were successfully manufactured through HME paired with dual-nozzle FDM 3D printing and demonstrated the power of 3D printing in developing multi-layer tablets with complex structures.

Formulation and evaluation of inhaled Sildenafil-loaded PLGA microparticles for treatment of pulmonary arterial hypertension (PAH): A novel high drug loaded formulation and scalable process via hot melt extrusion technology (Part â ).

In recent years, several techniques were employed to develop a local sustained pulmonary delivery of sildenafil citrate (SC) as an alternative for the intravenous and oral treatment of pulmonary arterial hypertension (PAH). Most of these methods, however, need to be improved due to limitations of scalability, low yield production, low drug loading, and stability issues. In this study, we report the use of hot-melt extrusion (HME) as a scalable process for making Poly (lactic-co-glycolic acid) (PLGA) microparticles with high SC load. The prepared particles were tested in vitro for local drug delivery to the lungs by inhalation. Sodium bicarbonate was included as a porogen in the formulation to make the particles more brittle and to impart favorable aerodynamic properties. Six formulations were prepared with different formulation compositions. Laser diffraction analysis was used to estimate the geometric particle size distribution of the microparticles. In-vitro aerodynamic performance was evaluated by the next-generation cascade impactor (NGI). It was reported in terms of an emitted dose (ED), an emitted fraction (EF%), a respirable fraction (RF%), a fine particle fraction (FPF%), a mass median aerodynamic diameter (MMAD), and geometric standard deviation (GSD). The formulations have also been characterized for surface morphology, entrapment efficiency, drug load, and in-vitro drug release. The results demonstrated that PLGA microparticles have a mean geometric particle size between 6 and 14 µm, entrapment efficiency of 77 to 89 %, and SC load between 17 and 33 % w/w. Fifteen percent of entrapped sildenafil was released over 24 h from the PLGA microparticles, and seventy percent over 7 days. The aerodynamic properties included fine particle fraction ranging between 19 and 33 % and an average mass median aerodynamic diameter of 6-13 µm.

Disulfiram 3D printed film produced via hot-melt extrusion techniques as a potential anticervical cancer candidate.

Cervical cancer is known globally as one of the most common health problems in women. Indeed, one of the most convenient approaches for its treatment is an appropriate bioadhesive vaginal film. This approach provides a local treatment modality, which inevitably decreases dosing frequency and improves patient compliance. Recently, disulfiram (DSF) has been investigated and demonstrated to possess anticervical cancer activity; therefore, it is employed in this work. The current study aimed to produce a novel, personalized three-dimensional (3D) printed DSF extended-release film using the hot-melt extrusion (HME) and 3D printing technologies. The optimization of the formulation composition and the HME and 3D printing processing temperatures was an important factor for overcoming the DSF heat-sensitivity issue. In addition, the 3D printing speed was specifically the most crucial parameter for alleviating heat-sensitivity concerns, which led to the production of films (F1 and F2) with an acceptable DSF content and good mechanical properties. The bioadhesion film study using sheep cervical tissue indicated a reasonable adhesive peak force (N) of 0.24 ± 0.08 for F1 and 0.40 ± 0.09 for F2, while the work of adhesion (N.mm) for F1 and F2 was 0.28 ± 0.14 and 0.54 ± 0.14, respectively. Moreover, the cumulative in vitro release data indicated that the printed films released DSF for up to 24 h. HME-coupled 3D printing successfully produced a patient-centric and personalized DSF extended-release vaginal film with a reduced dose and longer dosing interval.