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The primary focus of the research is to study the role of cocrystal and amorphous solid dispersion approaches for enhancing solubility and preserving the stability of a poorly soluble drug, i.e., ibuprofen (IBP). First, the solvent-assisted grinding approach determined the optimum molar ratio of the drug and the coformer (nicotinamide (NIC)). Later, the polymeric filaments of cocrystals and amorphous solid dispersions were developed using the hot melt extrusion (HME) process, and the printlets were fabricated using the fused deposition modeling (FDM) additive manufacturing process. In addition, the obtained filaments were also milled and compressed into tablets as reference samples. The formation of cocrystals and amorphous solid dispersions was evaluated and confirmed using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and powder X-ray diffraction (PXRD) analysis. The drug release profiles of 3D printlets with 50% infill were found to be faster and are in line with the release profiles of compressed tablets. In addition, the 3D-printed cocrystal formulation was stable for 6 months at accelerated conditions. However, the 3D printlets of amorphous solid dispersions and compressed tablets failed to retain stability attributed to the recrystallization of the drug and loss in tablet mechanical properties. This shows the suitability of a cocrystal platform as a novel approach for developing stable formulations of poorly soluble drug substances over amorphous solid dispersions., (© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

The current research aims to improve the solubility of the poorly soluble drug, i.e., ibuprofen, by developing self-emulsifying drug delivery systems (SEDDS) utilizing a twin screw melt granulation (TSMG) approach. Gelucire ® 44/14, Gelucire ® 48/16, and Transcutol ® HP were screened as suitable excipients for developing the SEDDS formulations. Initially, liquid SEDDS (L-SEDDS) were developed with oil concentrations between 20-50% w / w and surfactant to co-surfactant ratios of 2:1, 4:1, 6:1. The stable formulations of L-SEDDS were transformed into solid SEDDS (S-SEDDS) using a suitable adsorbent carrier and compressed into tablets (T-SEDDS). The S-SEDDS has improved flow, drug release profiles, and permeability compared to pure drugs. The existence of the drug in an amorphous state was confirmed by differential scanning calorimetry (DSC) and powder X-ray diffraction analysis (PXRD). The formulations with 20% w / w and 30% w / w of oil concentration and a 4:1 ratio of surfactant to co-surfactant have resulted in a stable homogeneous emulsion with a globule size of 14.67 ± 0.23 nm and 18.54 ± 0.55 nm. The compressed tablets were found stable after six months of storage at accelerated and long-term conditions. This shows the suitability of the TSMG approach as a single-step continuous manufacturing process for developing S-SEDDS formulations.

The objective of the current study is the formulation development and manufacturing of solid self-emulsifying drug delivery systems (HME S-SEDDS) via a single-step continuous hot-melt extrusion (HME) process. For this study, poorly soluble fenofibrate was selected as a model drug. From the results of pre-formulation studies, Compritol® HD5 ATO, Gelucire® 48/16, and Capmul® GMO-50 were selected as oil, surfactant and co-surfactant respectively for manufacturing of HME S-SEDDS. Neusilin® US2 was selected as a solid carrier. The design of experiments (response surface methodology) was employed to prepare formulations via a continuous HME process. The formulations were evaluated for emulsifying properties, crystallinity, stability, flow properties and drug release characteristics. The prepared HME S-SEDDS showed excellent flow properties, and the resultant emulsions were stable. The globule size of the optimized formulation was 269.6 nm. The DSC and XRD studies revealed the amorphous nature of the formulation and FTIR studies showed no significant interaction between fenofibrate and excipients. The drug release studies showed significant (p < 0.05) improvement in solubility compared to the pure drug (DE 15  = 45.04 for the optimized formulation), as >90% of drug release was observed within 15 min. The stability studies for the optimized formulation were conducted for 3 months at 40 °C/75% RH., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aqueous solubility is one of the key parameters for achieving the desired drug concentration in systemic circulation for better therapeutic outcomes. Carbamazepine (CBZ) is practically insoluble in water, is a BCS class II drug, and exhibits dissolution-dependent oral bioavailability. This study explored a novel application of hot-melt extrusion in the manufacture and development of a thermodynamically stable solid crystal suspension (SCS) to improve the solubility and dissolution rate of CBZ. The SCSs were prepared using sugar alcohols, such as mannitol or xylitol, as crystalline carriers. The drug-sugar blend was processed by hot melt extrusion up to 40 % (w/w) drug loading. The extruded SCS was evaluated for drug content, saturation solubility, differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) spectroscopy, powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), in vitro release, and stability studies. The physicochemical characterization revealed the highly crystalline existence of pure drug, pure carriers, and extruded SCS. FTIR analysis did not reveal any physical or chemical incompatibilities between the drug and sugar alcohols and showed a homogeneous CBZ distribution within respective crystalline carriers. The SEM micrographs of the solidified SCS revealed the presence of approximately 100 μm crystalline agglomerates. In vitro dissolution and solubility studies showed that the CBZ dissolution rate and solubility were improved significantly from both crystalline carriers for all tested drug loads. The SCSs showed no significant changes in drug content, in vitro release profiles, and thermal characteristics over 3 months of storage at accelerated stability conditions (40±2°C/75±5% RH). As a result, it can be inferred that the SCS strategy can be employed as a contemporary alternative technique to improve the dissolution rate of BCS class II drugs via HME technology., Competing Interests: Declaration of Interest The authors declare no conflict of interest.

The current research is focused on investigating the suitability of the twin screw melt granulation (TSMG) approach for improving the solubility of a non-steroidal anti-inflammatory (NSAIDs) drug (ibuprofen), by developing granules using lipid surfactants. The solubility of the drug within the solid lipid excipients (Gelucire® 48/16 and Gelucire® 50/13) was determined by differential scanning calorimetry (DSC). The formulations were developed for drug and lipid ratios of 1:1.5, 1:3, and 1:4.5 using Neusilin® US2 as a solid adsorbent carrier. The solid-state properties of the drug investigated using differential scanning calorimetry (DSC) have revealed the conversion of the drug to an amorphous form for 1:3 and 1:4.5 ratios of formulations confirmed by powder x-ray diffraction analysis (PXRD). Drug-excipient compatibility and formation of no interactions were characterized using Fourier transform infrared spectroscopy (FTIR). The granules with a 1:3 and 1:4.5 ratios of drug and lipid have improved drug dissolution and permeation, attributing to the formation of micellar emulsions. The stability of formulation with a 1:3 ratio of drug and lipid surfactant was preserved when stored in accelerated conditions. However, the formulation with a 1:4.5 ratio of drug and lipid failed to retain the amorphous state evidenced by the recrystallization of the drug. This shows the suitability of TSMG as a single-step continuous manufacturing process for developing melt granules to improve the solubility of poorly water-soluble drug substances., (© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Coupling hot-melt extrusion (HME) with fused deposition modeling three-dimensional printing (FDM-3DP) can facilitate the fabrication of tailored, patient-centered, and complex-shaped ocular dosage forms. We fabricated ciprofloxacin HCl ocular inserts by coupling high-throughput, solvent-free, and continuous HME with FDM-3DP. Insert fabrication utilized biocompatible, biodegradable, bioadhesive Klucel™ hydroxypropyl cellulose polymer, subjected to distinct FDM-3DP processing parameters, utilizing a design of experiment approach to achieve a tailored release profile. We determined the drug content, thermal properties, drug-excipient compatibility, surface morphology, in vitro release, antibacterial activity, ex-vivo transcorneal permeation, and stability of inserts. An inverse relationship was noted between insert thickness, infill density, and drug release rate. The optimized design demonstrated an amorphous solid dispersion with an extended-release profile over 24 h, no physical or chemical incompatibility, excellent mucoadhesive strength, smooth surface, lack of bacterial growth (Pseudomonas aeruginosa) in all release samples, and prolonged transcorneal drug flux compared with commercial eye drops and immediate-release inserts. The designed inserts were stable at room temperature considering drug content, thermal behavior, and release profile over three months. Overall, the fabricated insert could reduce administration frequency to once-daily dosing, affording a promising topical delivery platform with prolonged antibacterial activity and superior therapeutic outcomes for managing ocular bacterial infections., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Recent advances in drug delivery technologies utilizing a variety of carriers have resulted in a paradigm shift in the current approach to diagnosis and therapy. Mesoporous silica nanoparticles (MSNs) were developed in response to the need for materials with high thermal, chemical, and mechanical properties. The synthesis, ease of surface functionalization, tunable pore size, large surface area, and biocompatibility of MSNs make them useful in a variety of biomedical applications such as drug delivery, theranostics, and stem cell research. In addition, MSNs have a high capability of delivering actives ranging from small molecules such as drugs and amino acids to larger peptides, vaccines, and antibodies in general. Moreover, MSN-based transdermal delivery has sparked a lot of interest because of the increase in drug stability, permeation, and ease of functionalization. The functionalization of MSNs plays an important role in the efficient delivery of therapeutic agents in a highly controlled manner. This review introduced dermal and transdermal drug delivery systems, explained the anatomy of the skin, and summarized different barriers that affect the transdermal delivery of many therapeutic agents. In addition, the fundamentals of MSNs together with their physicochemical properties, synthesis approaches, raw materials used in their fabrication, and factors affecting their physicochemical properties will be covered. Moreover, the applications of MSNs in dermal and transdermal delivery, the biocompatibility of MSNs in terms of toxicity and safety, and biodistribution will be explained with the help of a detailed literature review. The review is covering the current and future perspectives of MSNs in the pharmaceutical field with therapeutic applications., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

This work developed high drug-load pellets for colon targeting in minimal steps by coupling hot-melt extrusion (HME) with a die-surface cutting pelletizer, offering a potential continuous pellet manufacturing process. Ketoprofen (KTP) was selected as a model drug for this study due to its thermal stability and severe upper gastrointestinal side effects. Low and high methoxyl grade pectins were the enzyme-triggered release matrix, and hydroxypropyl methylcellulose (HME 4 M/HME 100LV) was used as a premature release-retarding agent. The powder X-ray diffraction technique and the differential scanning calorimetry results revealed that KTP exists in the solid-solution state within the polymeric matrix after the HME step. The scanning electron micrographs of the fabricated pellets showed a smooth surface without any cracks. The lead formulation showed the lowest premature drug release (∼13%) with an extended KTP release profile over a 24 h period in the presence and absence of the release-triggering enzyme. The lead formulation was stable for 3 months at accelerated stability conditions (40 °C/75 ± 5% RH) concerning drug content, in vitro release, and thermal characteristics. In summary, coupling HME and pelletization processes could be a promising technology for developing colon-targeted drug delivery systems., Competing Interests: The authors believe that there are no conflicts of interest to declare for the research article entitled “Preparation and In vitro Evaluation of Hot-Melt Extruded Pectin-Based Pellets Containing Ketoprofen for Colon Targeting”., (© 2022 The Authors.)

The main objective of the current research was to investigate the effect of tablet shapes (heart-shaped and round tablets) and infill densities (50% and 100%) on the drug release profiles of 3D printed tablets prepared by hot-melt extrusion paired with fused deposition modeling techniques. Drug-loaded filaments of 1.5 mm and 2.5 mm diameters were extruded using a Process 11 mm hot-melt extruder employing atorvastatin calcium as a model drug and Kollicoat® IR, Kollidon® VA64, Kollidon® 12PF, and Kolliphor® P407 as hydrophilic polymers. Filaments of Kollicoat® IR in combination with Kollidon® VA64/Kollidon® 12PF has resulted in successful printing of immediate release tablets. The mechanical properties of drug-loaded filaments were evaluated using a 3-point bend test and stiffness test. The transformation of a crystalline drug to an amorphous form and the absence of drug-polymer interactions were confirmed by differential scanning calorimetry and Fourier transform infrared spectroscopy, respectively. The effect of infill density on drug release profiles was greater than that of tablet shape. The stability of 3D printed tablets was preserved even after storage under accelerated conditions (40 ± 2°C and 75 ± 5% RH) for 6 months. Thus, the 3D printing process of hot-melt extrusion paired with fused deposition modeling serves as an alternative manufacturing approach for developing patient-focused doses., (© 2022. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

The surface drying process is an important technology in the pharmaceutical, biomedical, and food industries. The final stage of formulation development (i.e., the drying process) faces several challenges, and overall mastering depends on the end step. The advent of new emerging technologies paved the way for commercialization. Thin film freezing (TFF) is a new emerging freeze-drying technique available for various treatment modalities in drug delivery. TFF has now been used for the commercialization of pharmaceuticals, food, and biopharmaceutical products. The present review highlights the fundamentals of TFF along with modulated techniques used for drying pharmaceuticals and biopharmaceuticals. Furthermore, we have covered various therapeutic applications of TFF technology in the development of nanoformulations, dry powder for inhalations and vaccines. TFF holds promise in delivering therapeutics for lung diseases such as fungal infection, bacterial infection, lung dysfunction, and pneumonia.

The development of amorphous solid dispersions (ASDs) of high-melting-point drug substances using hot-melt extrusion (HME) continues to be challenging because of the limited availability of polymers that are stable at high processing temperatures. The main aim of this research project is to improve processability and develop three-dimensional (3D) cocrystal printlets of hydrochlorothiazide (HCTZ) using HME paired fused deposition modeling (FDM) techniques. Among the investigated coformers, nicotinamide (NIC) was identified as a suitable coformer. The cocrystal filaments of HCTZ-NIC and pure HCTZ that were suitable for the FDM 3D-printing process were developed using a Process 11 mm Twin -Screw Extruder with Kollicoat® IR and Kollidon® VA64 as polymeric carriers. The investigation of extruded filaments using differential scanning calorimetry (DSC) revealed the formation of HCTZ-NIC cocrystals, which was further confirmed using Fourier transform infrared spectroscopy (FTIR) and powder X-ray diffraction analysis (PXRD). The 3D-printed printlets of HCTZ-NIC with 50 % infill density resulted in improved dissolution and permeability compared to pure drug. This demonstrates the suitability of the HME-paired FDM 3D-printing technique for improving solubility and developing on-demand patient-focused dosage forms for poorly soluble high-melting-point drug substances by utilizing a cocrystal approach., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Solid lipid nanoparticles (SLNs) are an alternate carrier system to liposomes, polymeric nanoparticles, and inorganic carriers. SLNs have attracted increasing attention in recent years for delivering drugs, nucleic acids, proteins, peptides, nutraceuticals, and cosmetics. These nanocarriers have attracted industrial attention due to their ease of preparation, physicochemical stability, and scalability. These characteristics make SLNs attractive for manufacture on a large scale. Currently, several products with SLNs are in clinical trials, and there is a high possibility that SLN carriers will quickly increase their presence in the market. A large-scale manufacturing unit is required for commercial applications to prepare enough formulations for clinical studies. Furthermore, continuous processing is becoming more popular in the pharmaceutical sector to reduce product batch-to-batch differences. This review paper discusses some conventional methods and the rationale for large-scale production. It further covers recent progress in scale-up methods for the synthesis of SLNs, including high-pressure homogenization (HPH), hot melt extrusion coupled with HPH, microchannels, nanoprecipitation using static mixers, and microemulsion-based methods. These scale-up technologies enable the possibility of commercialization of SLNs. Furthermore, ongoing studies indicate that these technologies will eventually reach the pharmaceutical market.

With the growing burden of cancer, parallel advancements in anticancer nanotechnological solutions have been witnessed. Among the different types of cancers, breast cancer accounts for approximately 25% and leads to 15% of deaths. Nanomedicine and its allied fields of material science have revolutionized the science of medicine in the 21st century. Novel treatments have paved the way for improved drug delivery systems that have better efficacy and reduced adverse effects. A variety of nanoformulations using lipids, polymers, inorganic, and peptide-based nanomedicines with various functionalities are being synthesized. Thus, elaborate knowledge of these intelligent nanomedicines for highly promising drug delivery systems is of prime importance. Polymeric micelles (PMs) are generally easy to prepare with good solubilization properties; hence, they appear to be an attractive alternative over the other nanosystems. Although an overall perspective of PM systems has been presented in recent reviews, a brief discussion has been provided on PMs for breast cancer. This review provides a discussion of the state-of-the-art PMs together with the most recent advances in this field. Furthermore, special emphasis is placed on regulatory guidelines, clinical translation potential, and future aspects of the use of PMs in breast cancer treatment. The recent developments in micelle formulations look promising, with regulatory guidelines that are now more clearly defined; hence, we anticipate early clinical translation in the near future.

Among various drug administration routes, oral drug delivery is preferred and is considered patient-friendly; hence, most of the marketed drugs are available as conventional tablets or capsules. In such cases, the administration of drugs with or without food has tremendous importance on the bioavailability of the drugs. The presence of food may increase (positive effect) or decrease (negative effect) the bioavailability of the drug. Such a positive or negative effect is undesirable since it makes dosage estimation difficult in several diseases. This may lead to an increased propensity for adverse effects of drugs when a positive food effect is perceived. However, a negative food effect may lead to therapeutic insufficiency for patients suffering from life-threatening disorders. This review emphasizes the causes of food effects, formulation strategies to overcome the fast-fed variability, and the regulatory aspects of drugs with food effects, which may open new avenues for researchers to design products that may help to eliminate fast-fed variability.

Amorphous solid dispersions (ASDs) have gained attention as a formulation strategy in recent years, with the potential to improve the apparent solubility and, hence, the oral bioavailability of poorly soluble drugs. The process of formulating ASDs is commonly faced with challenges owing to the intrinsic physical and chemical instability of the initial amorphous form and the long-term physical stability of drug formulations. Numerous research publications on hot-melt extrusion (HME) technology have demonstrated that it is the most efficient approach for manufacturing reasonably stable ASDs. The HME technique has been established as a faster scale-up production strategy for formulation evaluation and has the potential to minimize the time to market. Thermodynamic evaluation and theoretical predictions of drug-polymer solubility and miscibility may assist to reduce the product development cost by HME. This review article highlights robust and established prediction theories and experimental approaches for the selection of polymeric carriers for the development of hot melt extrusion based stable amorphous solid dispersions (ASDs). In addition, this review makes a significant contribution to the literature as a pilot guide for ASD assessment, as well as to confirm the drug-polymer compatibility and physical stability of HME-based formulations., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Wound healing is highly specialized dynamic multiple phase process for the repair of damaged/injured tissues through an intricate mechanism. Any failure in the normal wound healing process results in abnormal scar formation, and chronic state which is more susceptible to infections. Chronic wounds affect patients' quality of life along with increased morbidity and mortality and are huge financial burden to healthcare systems worldwide, and thus requires specialized biomedical intensive treatment for its management. The clinical assessment and management of chronic wounds remains challenging despite the development of various therapeutic regimens owing to its painstakingly long-term treatment requirement and complex wound healing mechanism. Various conventional approaches such as cell therapy, gene therapy, growth factor delivery, wound dressings, and skin grafts etc., are being utilized for promoting wound healing in different types of wounds. However, all these abovementioned therapies are not satisfactory for all wound types, therefore, there is an urgent demand for the development of competitive therapies. Therefore, there is a pertinent requirement to develop newer and innovative treatment modalities for multipart therapeutic regimens for chronic wounds. Recent developments in advanced wound care technology includes nanotherapeutics, stem cells therapy, bioengineered skin grafts, and 3D bioprinting-based strategies for improving therapeutic outcomes with a focus on skin regeneration with minimal side effects. The main objective of this review is to provide an updated overview of progress in therapeutic options in chronic wounds healing and management over the years using next generation innovative approaches. Herein, we have discussed the skin function and anatomy, wounds and wound healing processes, followed by conventional treatment modalities for wound healing and skin regeneration. Furthermore, various emerging and innovative strategies for promoting quality wound healing such as nanotherapeutics, stem cells therapy, 3D bioprinted skin, extracellular matrix-based approaches, platelet-rich plasma-based approaches, and cold plasma treatment therapy have been discussed with their benefits and shortcomings. Finally, challenges of these innovative strategies are reviewed with a note on future prospects.

Fixed-dose combinations (FDCs) achieve optimal goals for treatment with minimal side effects, decreased administration of large number of tablets, thus, greater convenience, and improved patient compliance. However, conventional FDCs do not have a guaranteed place in the future of patient-centered drug development because of the difficulty in achieving dose titration of each drug for individualized specific health needs and desired therapeutic outcomes. In the current study, FDCs of two antihypertensive drugs were fabricated with two distinct compartments using fused deposition modeling three-dimensional printing (FDM-3DP). Atorvastatin calcium and Amlodipine besylate loaded filaments were prepared by hot-melt extrusion. Shell-core FDC tablets were designed to have different infills for individualized dosing. Differential scanning calorimetry and powder X-ray diffraction revealed that both drugs were transformed into amorphous forms within the polymeric carriers. The fabricated tablets met the United States Pharmacopeia acceptance criteria for friability, content uniformity, and dissolution testing. The fabricated tablets were stable at room temperature with respect to drug content and thermal behavior over six months. This dynamic dosage form provides flexibility in dose titration and maintains the advantages of FDCs, thus achieving optimal therapeutic outcomes in different healthcare facilities., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Crystal engineering is an emerging tool for altering the physicochemical properties of drug candidates. The objective of the current investigation was to develop cocrystals of hydrochlorothiazide (HCT) with coformers such as nicotinamide (NIC), resorcinol (RSL), and catechol (CAT) using hot-melt extrusion (HME) technology. The liquid-assisted grinding (LAG) method was used to prepare cocrystals by grinding the drug and coformer in a definite molar ratio as a reference and to check the feasibility of cocrystal formation. Cocrystals were prepared using HME and evaluated with differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffractometry, and scanning electron microscopy and compared with LAG cocrystals. Barrel temperature was the critical process parameter for producing high-quality cocrystals in HME. All cocrystals exhibited improved solubility compared to the native drug, and HCT-NIC cocrystals showed a two-fold increase in solubility. Similarly, HCT-RSL and HCT-CAT showed higher solubility profiles and improved diffusion/permeability characteristics compared to that of the pure HCT due to the drug-coformer interactions in the cocrystals. In this study, the solubility of the coformer was the key factor determining cocrystal solubilization. However, hot-melt extrusion is an alternative technology for creating pharmaceutical cocrystals and has potential for industrial scale-up., (© 2022. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Dose dumping is the major drawback of sustained release (SR) matrices. The current research aimed to develop the stable lipid-based SR matrices of quetiapine fumarate (QTF) using Geleol™ (glyceryl monostearate; GMS) as the lipid matrix carrier and Klucel™ EF (HPC EF), Kollidon ® VA64, and Kollidon ® 12PF as hydrophilic binders. Formulations were developed using advanced twin screw melt granulation (TSMG) approach and the direct compression (DC) technique. Compared with the blends of DC, the granules of TSMG exhibited improved flow properties and tabletability. Solid-state characterization by differential scanning calorimetry of the prepared granules exhibited the crystalline nature of the lipid. Fourier transform infrared spectroscopy demonstrated no interaction between the formulation ingredients. The compressed matrices of TSMG and DC resulted in the sustained release of a drug over 16-24 h. Upon storage under accelerated conditions for 6 months, the matrices of TSMG retained their sustained release characteristics with no dose dumping in alcohol, whereas the matrices of DC resulted in the dose dumping of the drug attributing to the loss of matrix integrity and phase separation of lipid. Thus, it is concluded that the uniform distribution of a softened binder into a molten lipid carrier results in the stable matrices of TSMG., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or conflicts of interest

Interest in 3D printing for pharmaceutical applications has increased in recent years. Compared to other 3D printing techniques, hot melt extrusion (HME)-based fused deposition modeling (FDM) 3D printing has been the most extensively investigated for patient-focused dosage. HME technology can be coupled with FDM 3D printing as a continuous manufacturing process. However, the crucial pharmaceutical polymers, formulation and process parameters must be investigated to establish HME-coupled FDM 3D printing. These advancements will lead the way towards developing continuous drug delivery systems for personalized therapy. This brief overview classifies pharmaceutical additive manufacturing, Hot Melt Extrusion, and Fused Deposition Modeling 3D printing techniques with a focus on coupling HME and FDM 3D printing processes. It also provides insights on the critical material properties, process and equipment parameters and limitations of successful HME-coupled FDM systems., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The objective of this study was to enhance dissolution and permeation of a low soluble, absorbable fexofenadine hydrochloride (FFH) by preparing solid dispersions using polyethylene glycol 20,000 (PEG 20,000) and poloxamer 188 as carriers. The phase solubility measurement for the supplied FFH revealed a linear increase in the solubility of fexofenadine with increasing carrier concentration in water (1.45 mg/mL to 11.78 mg/mL with 0% w/v to 30% w/v PEG 20,000; 1.45 mg/mL to 12.27 mg/mL with 0% w/v to 30% w/v poloxamer 188). To select the appropriate drug carrier concentration, a series of solid dispersions were prepared in the drug carrier weight ratios of 1:1, 1:2 and 1:4 by fusion method. The solid dispersions composed of drug carrier at 1:4 weight ratio showed highest dissolution with the time required for the release of 50% of the drug <15 min compared to the supplied FFH (>120 min). The intestinal absorption study presented a significant improvement in the absorption of drug from the solid dispersions composed of poloxamer 188 than PEG 20,000. In summary, the solid dispersions of FFH prepared using PEG 20,000 and poloxamer 188 demonstrated improved dissolution and absorption than supplied FFH and could be used to improve the oral bioavailability of fexofenadine.

Enhancing the solubility of active drug ingredients is a major challenge faced by scientists and researchers. Different approaches have been explored for the enhancement of solubility and physicochemical properties of drugs, without affecting their stability or pharmacological activity. Among the various strategies available, pharmaceutical co-crystals, co-amorphous systems, and pharmaceutical salts as multicomponent systems (MCS) have gained interest to improve physicochemical properties of drugs. Development of MCS by conventional methods involves the utilization of excess amount of solvents, thus, making the product prone to instability, and may also cause harmful side effects in patients. Scale up is critical and involves the investment of huge capital and time. Lately, hot-melt extrusion has been utilized in the development of MCS to enhance solubility, bioavailability, stability, and physicochemical properties of the drugs. In this review, the authors discussed the development of different MCS produced via hot-melt extrusion technology. Specifically, approaches for screening of co-formers and co-crystals, selection of excipients for co-amorphous systems, pharmaceutical salts, and significance of MCS and process parameters affecting product quality are discussed., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

The misuse, abuse, and illicit use of prescription opioid analgesics is a global public health concern. However, there are many viable therapeutic options for the treatment of patients with chronic pain. Both intact and manipulated opioid drug products are abused by various routes such as oral, nasal, and injection, which may lead to overdose, drug addiction, and even death. To combat the abuse of these medications, regulatory agencies and pharmaceutical companies are switching their interest towards developing Abuse Deterrent Formulations (ADFs), with the intent to deter the abuse of opioid products to a maximum extent. There are several manufacturing strategies implemented in an attempt to develop ADFs. An example includes matrix tablets of high molecular weight polymers such as polyethylene oxide. The scalable and continuous manufacturing techniques, such as Hot-Melt Extrusion (HME), is increasingly accepted by pharmaceutical companies to advance the development and manufacturing of ADFs. The application of the HME technique in the development of ADFs may overcome the challenges of opioid analgesic formulation development and provide improved protection against misuse and abuse, while also ensuring access to safe and effective use in patients with chronic pain. This review deals with a brief overview of strategies, with emphasis on HME to deter opioid abuse, in vitro characterization methods, commonly used excipients in the development of ADFs, and regulatory standards to meet the requirements of ADFs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Three-dimensional printing could serve as a platform to fabricate individualized medicines and complex-structured solid dosage forms. Herein, hot melt extrusion was coupled with 3D printing to develop a unique gastro retentive dosage form to personalize treatment of cinnarizine or other narrow absorption window drugs. The mechanical strength of the extruded strands was optimized for printing by combining two polymers, hydroxypropyl cellulose and vinylpyrrolidone vinyl acetate copolymer. The unit dose, floating force, and release profile were controlled by the printing parameters and object design. The tablets floated immediately within the FaSSGF, and floating force was relatively constant up to 12 h. Drug release followed zero-order kinetics and could be controlled from 6 h to ≥ 12 h. Input variables had a good correlation (R > 0.95) with unit dose, floating force, and dissolution profile (p < 0.05). Authors successfully proposed and tested a new paradigm of individualized medicine fabrication to meet individual patient needs., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Hot melt extrusion has been an exciting technology in the pharmaceutical field owing to its novel applicability. Twin-screw granulation presents a great potential and offers many advantages relative to conventional granulation processes. Different twin-screw granulation techniques, such as twin-screw dry granulation, twin-screw wet granulation, and twin-screw melt granulation, are currently being developed as robust and reproducible granulation processes. The competence of twin-screw granulation as a continuous manufacturing process has contributed to its suitability as an alternative granulation option within the pharmaceutical industry. In this article, different types of twin-screw granulation techniques were discussed. In addition, the screw elements, scale-up process, continuous twin-screw granulation which involves process analytical tools, and excipients were explored. This economical, industrially scalable process can be automated for continuous manufacturing to produce granules for the development of oral solid dosage forms. However, extensive research using process analytical tools is warranted to develop processes for the continuous manufacture of granules., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)