Panobinostat is a highly active and potent non-selective histone deacetylase inhibitor (HDACi) that demonstrates significant anticancer activity against various cancers, including pancreatic cancer. However, like other HDAC inhibitors, its anticancer efficacy is often limited due to factors such as hydrophobicity, non-specificity to tumor cells, and poor pharmacokinetics. To overcome these limitations, encapsulating panobinostat in nanocarriers can enhance controlled drug release and increase cellular uptake, thereby improving therapeutic efficacy. In this study, bovine serum albumin (BSA) was utilized as a nanomaterial due to its nontoxicity, biocompatibility, and biodegradability. Initially, various drug-to-polymer ratios were tested to determine the optimal ratio for efficient loading and encapsulation. The BSA nanocarriers were prepared through a self-assembly method, and a drug-to-polymer ratio of 1:2.5 resulted in the highest loading and encapsulation efficiencies of 19.9% and 47.7%, respectively. The hydrodynamic diameter and zeta potential of the optimized nanoparticles were measured at 224.9 ± 5.0 nm and -28.6 ± 0.8 mV, respectively. Results from various physicochemical tests, including FTIR, XRD, DSC, and CD, confirmed the stability of the panobinostat-loaded nanocarriers. In vitro cytotoxicity studies indicated that nanoencapsulation significantly enhanced the anticancer efficacy of panobinostat compared to its free form.

Gemcitabine is a powerful anticancer antimetabolite drug which is usually administered as hydrochloride salt (GemHCl), but its systemic administration is accompanied by the undesirable "burst" phenomenon and its adverse side effects. To avoid the "burst", drugs can be encapsulated on suitable matrices to yield a local and delayed release. Here, GemHCl was encapsulated on aluminum metal-organic framework MOF-253 by liquid-assisted grinding (LAG) to form a new pharmaceutical composite. In the composite, the bonding was determined by the complementary ATR-FTIR spectroscopy, solid-state NMR (SS-NMR) spectroscopy and powder XRD. The interactions "drug-matrix" proceed by the C-N group of GemHCl drug and the bipyridyl unit of linker in MOF-253 matrix. Next, a powder of the composite was processed to obtain a mechanically pressed robust pharmaceutical pellet. The pellet was further tested for the delayed release of gemcitabine to phosphate buffered saline (PBS) at 37 ℃ using an automated drug dissolution system (ADDS). The pellet of the composite is found to be stable in PBS, and it shows delayed drug release up to 5 days without the "burst", in contrast to the pellet of GemHCl which quickly dissolves. Next, in the viability tests of pancreatic cancer cells PANC-1 by the Alamar Blue fluorescence assay in the 72 h. timescale, the composite is found to be more toxic than GemHCl. Finally, the prolonged toxicity of the released gemcitabine to PANC-1 cells was investigated by continuous measurements of proliferation (growth) for 6 days, using xCELLigence Real Time Cell Analyzer (RTCA). At higher concentrations and longer times, the composite is more effective than pure GemHCl, consistently with delayed drug release from the former. The encapsulation of GemHCl on MOFs by the means of mechano-chemistry constitutes a new and promising approach for the preparation of advanced functional composites for controlled, delayed and local drug release, and their potential use in the anticancer drug-eluting implants.

Whether it be due to genetic variances, lack of patient adherence, or sub-optimal drug metabolism, the risk of antibiotic resistance from medications administered systemically continues to pose significant challenges to fighting infectious diseases. Ideally, infections would be treated locally for maximal efficacy while minimizing off-target effects. The electrospinning of biomaterials has recently facilitated the creation of electrospun nanofibers as an alternative delivery vehicle for local treatment. This review describes electrospun nanofiber applications to locally target various infectious diseases. Electrospinning is first reviewed as a method to fabricate nanofiber platforms with advantageous properties for developing drug delivery systems. The emergence of artificial intelligence to facilitate the development of nanofiber formulations and the evaluation of operating parameters to customize therapeutic behavior are described. A range of biomaterials utilized for electrospinning nanofibers is summarized in the context of properties suitable for drug delivery, particularly to treat infectious diseases. The current body of literature for electrospun nanofiber applications to tackle infectious diseases, including sexually transmitted infections, oral infections, and infections is described. We anticipate that the advantages of electrospun nanofibers to facilitate targeted application while minimizing antibiotic resistance will substantially expand their clinical use in coming years.

Macrophages are an integral part of the innate immune system and act as a first line of defense to pathogens; however, macrophages can be reservoirs for pathogens to hide and replicate. Tuberculosis, influenza virus, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are common diseases whose pathogens are uptaken into macrophages. Current treatments for diseases such as these are limited by the therapeutic delivery method, which typically involves systemic delivery in large, frequent doses. This study aims to overcome this limitation via the development of an inhalable dry powder microparticle (MP) formulation capable of targeted drug delivery to alveolar macrophages in addition to controlled release of a therapeutic. A simple one-step spray drying method was used to synthesize acetalated dextran (Ac-Dex) MP loaded with the model therapeutic, curcumin, and 1,2-dipalmitoyl-sn-glycero-3-phospho--serine (DPPS), which is a phospholipid that induces ligand-receptor mediated macrophage phagocytosis. The resulting MP exhibited significantly more uptake by RAW 264.7 macrophages in comparison to MP without DPPS, and it was shown that DPPS-mediated uptake was macrophage specific. The particles exhibited pH-responsive release and aerosol dispersion analysis confirmed the MP can be effectively aerosolized for pulmonary delivery. Overall, the described MP has the potential to improve treatment efficacy for macrophage-associated diseases.

Tamoxifen (TMF) is an anticancer agent used for managing estrogen receptor-positive breast cancer. It has limited therapeutic efficacy against breast cancer, which could be enhanced by the coadministration of herbal drugs like piperine (PIP). However, the hydrophobic nature of TMF and PIP restricts their therapeutic application. Therefore, the present study focuses on the impact of the anticancer activity of TMF in combination with PIP and after entrapping them into liposomes (TMF-PIP-LPs and TMF-PIP-PEG-LPs). The liposomes were prepared using the thin film hydration method. In addition, the morphology of the prepared liposomes was found spherical after SEM and TEM analyses. Further, the cytotoxicity (IC) study of pure PIP and TMF was found to be 90.3 ± 10.2 μg/mL and 40.9 ± 5.9 μg/mL, respectively. Interestingly, an improved cytotoxicity (IC) was observed when the TMF and PIP were loaded into liposomes (TMF-PIP-LPs: 21 ± 1.6 μg/mL and TMF-PIP-PEG-LPs: 10 ± 0.5 μg/mL). Also, the PEGylated liposomes showed improvement in cellular uptake as compared to liposomes without PEGylation in MCF-7 human breast carcinoma cells. Thus, the enhanced cellular uptake and improved cytotoxicity of PEGylated liposomes can be a suitable strategy for delivering TMF with PIP for breast cancer treatment.

Intercellular adhesion molecule 1 (ICAM-1) is a cell-surface protein actively explored for targeted drug delivery. Anti-ICAM-1 nanocarriers (NCs) target ICAM-1-positive sites after intravenous injection in animal models, but quantitative mechanistic examination of cellular-level transport in vivo is not possible. Prior studies in human cell cultures indicated efficient uptake of these formulations via cell adhesion molecule-(CAM)-mediated endocytosis. However, ICAM-1 sequence differs among species; thus, whether anti-ICAM-1 NCs induce similar behavior in animal cells, key for intracellular drug delivery, is unknown. To begin bridging this gap, we first qualitatively verified intracellular transport of anti-ICAM-1 NCs in vivo and then developed new cellular models expressing ICAM-1 from mouse, dog, pig, and monkey, species relevant to pharmaceutical translation and veterinary medicine. ICAM-1 expression was verified by flow cytometry and confocal microscopy. These cells showed specific targeting compared to IgG NCs or cells treated with anti-ICAM-1 blocker. Anti-ICAM-1 NCs entered cells in a time- and temperature-dependent manner, with kinetics and pathway compatible with CAM-mediated endocytosis. All parameters tested were strikingly similar to those from human cells expressing ICAM-1 endogenously. Therefore, this new cellular platform represents a valuable tool that can be used in parallel to support in vivo studies on ICAM-1-targeted NCs during pharmaceutical translation.

Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults. Despite aggressive surgical and medical treatments, the prognosis for patients with GBM remains grim and tumor recurrence is inevitable. Long-acting localized chemotherapy can not only reduce systemic toxicity, but also maintain chemotherapeutic concentration at the tumor sites over prolonged duration, thereby having the potential to improve GBM treatment. The present research aims to investigate an injectable in situ hydrogel made up of biopolymers collagen and hyaluronic acid that are abundant in the brain for sustained chemotherapy against GBM. Temozolomide (TMZ), an alkylating antineoplastic agent and the first-line treatment for GBM, was selected as the model chemotherapeutic and encapsulated in liposomes to facilitate deep tumor penetration. Whether the presence of liposomes affected gelling behavior and rheological properties of the collagen-based hydrogel system was investigated. Moreover, the in vitro efficacy of the TMZ-liposome/hydrogel composite was studied using a 3D spheroid GBM model. The developed TMZ-liposome/hydrogel composite gelled within 1 min at 37 °C and demonstrated sustained payload release and deep tumor penetration in the 3D GBM spheroids. More importantly, the composite remarkably inhibited glioma cell growth. These results showed that the developed liposome/in situ hydrogel composite is a promising drug delivery platform for the long-term localized treatment of GBM.

Obesity is a severe public health problem. Healthy lifestyle interventions are commonly recommended for fighting obesity. But they are hard to follow and have low efficacy. Pharmacotherapy and surgery are of high efficacy but are beset with side effects. Browning subcutaneous white adipose tissue (WAT) is a practical and efficient approach for combating obesity. Metformin, a commonly used FDA-approved antidiabetic drug, is potent to induce browning of WAT through phosphorylation and activation of AMP-activated protein kinase. However, oral administration of metformin has low oral bioavailability, fast renal clearance, and low target specificity that limit metformin's application in browning WAT. Local and transdermal delivery of metformin directly to subcutaneous WAT using injection or microneedle (MN) in combination with iontophoresis (INT) may solve these problems. In this paper, we administered metformin to C57BL/6J obese mice using the following three routes: transdermal delivery (MN and INT), local injection into inguinal WAT (IgWAT, a type of subcutaneous WAT in mice), and oral gavage. The anti-obesity and metabolic effects of metformin via these delivery routes were determined and compared. As compared to local IgWAT injection and oral gavage delivery, transdermal delivery of metformin using MN and INT resulted in 9% lower body weight and 7% decrease in body fat% accompanied by improved energy metabolism and decreased inflammation through browning IgWAT in obese C57BL/6J mice. Transdermal delivery of metformin using MN and INT is an effective approach in browning subcutaneous WAT for combating obesity and improving metabolic health.

Natural medicinal compounds (NMCs) can assist effectively in treating bone disorders. NMC release kinetics from a ceramic bone tissue engineering scaffold can be tailored. However, inferior physicochemical properties halt their therapeutic applications and need a carrier system for delivery. We developed a multi-functionalized scaffold to understand the effect of curcumin (Cur) and resveratrol (Rsv) on biological properties. Polycaprolactone (PCL) nanoparticles encapsulated resveratrol in the polymeric matrix. Nanoparticles showed a hydrodynamic diameter of about 180 nm, - 16 mV zeta potential, and up to ~65 % encapsulation efficiency. Scaffolds made of zinc-doped tricalcium phosphate (Zn-TCP) were coated with curcumin followed by either resveratrol (Cur-Rsv) or resveratrol nanoparticles (Cur-Rsv-NP). NMC-loaded scaffolds exhibited a biphasic release pattern over 60 days. Solubility and hydrophobic-hydrophilic interactions affected the NMC release profile. Resveratrol showed rapid release as compared to curcumin. The treated scaffold increased the cell viability of human fetal osteoblast (hFOB) by 1.8-fold as compared to the control. It exhibited a 6-fold increase in cytotoxicity toward osteosarcoma (MG-63) cells as compared to the untreated scaffold. NMCs loaded scaffold effectively inhibited from colonizing over the scaffold. Zinc doping enhanced osteoblast growth and prevented bacterial colony formation. Such design principle provided a direction for developing multi-functionalized calcium phosphate (CaP) scaffolds against bone diseases for orthopedic applications.

Topical antimicrobial treatments for severe burns and chronic wounds provide effective treatment against infections, but cause pain and discomfort with application. This study aimed to develop an antimicrobial topical formulation comprising thermoreversible poloxamers (Pluronic F127 and F68) and a broad-spectrum antimicrobial agent (ciprofloxacin hydrochloride, CH), that could be sprayed to eliminate application pain while maintaining antimicrobial activity. Formulations were characterized to determine their sprayability under cold conditions, gelation temperature, final storage modulus at skin temperature, drug release profile, permeation through impaired porcine skin, and inhibition against common bacterial pathogens that colonize wounds. All cold formulations were sprayable from simple hand-held, pump-action sprayers due to their low viscosity. Upon heating, 17 and 20% Pluronic F127 formulations produced hydrogels eight to ten degrees below skin temperature, independent of ciprofloxacin loading. Increasing concentrations of Pluronic F127 increased the final storage modulus and viscosity of the gels, while inclusion of Pluronic F68 reduced these properties, showing that hydrogel rheological properties at skin temperature can be tuned via choice of formulation. Drug release was directly correlated to the rheological properties, with stiffer gels resulting in a decrease in drug release rate. Overall, gels released about 65-90% of their load within 12 hours. skin permeation demonstrated that drug was well retained in impaired porcine skin, which is desired to continuously treat bacteria localized to the wound. A well-diffusion assay indicated that the hydrogels had greater bacterial inhibition against , , and two strains of when compared to commercial controls. Overall, the results show the potential of CH-loaded poloxamer formulations as suitable sprayable topical dressings to deliver antimicrobials directly to wounds.

In every century of history, there are many new diseases emerged, which are not even cured by many developed countries. Today, despite of scientific development, new deadly pandemic diseases are caused by microorganisms. Hygiene is considered to be one of the best methods of avoiding such communicable diseases, especially viral diseases. Illness caused by SARS-CoV-2 was termed COVID-19 by the WHO, the acronym derived from "coronavirus disease 2019. The globe is living in the worst epidemic era, with the highest infection and mortality rate owing to COVID-19 reaching 6.89% (data up to March 2023). In recent years, nano biotechnology has become a promising and visible field of nanotechnology. Interestingly, nanotechnology is being used to cure many ailments and it has revolutionized many aspects of our lives. Several COVID-19 diagnostic approaches based on nanomaterial have been developed. The various metal NPs, it is highly anticipated that could be viable and economical alternatives for treating drug resistant in many deadly pandemic diseases in near future. This review focuses on an overview of nanotechnology's increasing involvement in the diagnosis, prevention, and therapy of COVID-19, also this review provides readers with an awareness and knowledge of importance of hygiene.

Deficiency of selenium (Se) has been described in a significant number of COVID-19 patients having a higher incidence of mortality, which makes it a pertinent issue to be addressed clinically for effective management of the COVID-19 pandemic. Se nanoparticles (SeNPs) provide a unique option for managing the havoc caused by the COVID-19 pandemic. SeNPs possess promising anti-inflammatory and anti-fibrotic effects by virtue of their nuclear factor kappa-light-chain-stimulator of activated B cells (NFκB), mitogen-activated protein kinase (MAPKs), and transforming growth factor-beta (TGF-β) modulatory activity. In addition, SeNPs possess remarkable immunomodulatory effects, making them a suitable option for supplementation with a much lower risk of toxicity compared to their elemental counterpart. Further, SeNPs have been shown to curtail viral and microbial infections, thus, making it a novel means to halt viral growth. In addition, it can be administered in the form of aerosol spray, direct injection, or infused thin-film transdermal patches to reduce the spread of this highly contagious viral infection. Moreover, a considerable decrease in the expression of selenoprotein along with enhanced expression of IL-6 in COVID-19 suggests a potential association among selenoprotein expression and COVID-19. In this review, we highlight the unique antimicrobial and antiviral properties of SeNPs and the immunomodulatory potential of selenoproteins. We provide the rationale behind their potentially interesting properties and further exploration in the context of microbial and viral infections. Further, the importance of selenoproteins and their role in maintaining a successful immune response along with their association to Se status is summarized.

Cervical cancer remains a significant global health challenge, and there is a need for innovative drug delivery systems to improve the efficacy of anticancer drugs. In this study, we developed and evaluated boronated chitosan/alginate nanoparticles (BCHIALG NPs) as a localized mucoadhesive drug delivery system for cervical cancer. Boronated chitosan (BCHI) was synthesized by incorporating 4-carboxyphenylboronic acid onto chitosan (CHI), and boronated chitosan/alginate nanoparticles (BCHIALG NPs) with varying polymer ratios were prepared using an ionic gelation method. The physical properties, drug loading capacity/encapsulation efficiency, mucoadhesive properties, and drug release profile of the nanoparticles were evaluated. The BCHIALG NPs exhibited a size of less than 390 nm and demonstrated high drug encapsulation efficiency (98.1 - 99.8%) and loading capacity (326.9 - 332.7 μg/mg). Remarkably, the BCHIALG NPs containing 0.03% boronated chitosan and 0.07% alginate showed superior mucoadhesive capability compared to CHIALG NPs, providing sustained drug release and they showed the most promising results as a transmucosal drug delivery system for hydrophobic drugs like paclitaxel (PTX). To the best of our knowledge, this is the first report investigating BCHIALG NPs for cervical drug delivery. The new mucoadhesive paclitaxel formulation could offer an innovative strategy for improving cervical cancer treatment.

[This corrects the article DOI: 10.1016/j.jddst.2022.103921.].

Inhalation phage therapy is proposed as a replacement approach for antibiotics in the treatment of pulmonary bacterial infections. This study investigates phage therapy on bacterial pneumonia in patients with moderate to severe COVID-19 via the inhalation route. In this double-blind clinical trial, 60 patients with positive COVID-19 hospitalized in three central Mazandaran hospitals were chosen and randomly divided into two intervention and control groups. Standard country protocol drugs plus 10 mL of phage suspension every 12 h with a mesh nebulizer was prescribed for 7 days in the intervention group. The two groups were compared in terms of OSat, survival rate, severe secondary pulmonary bacterial infection and duration of hospitalization. Comparing the results between the intervention and control group, in terms of the trend of OSat change, negative sputum culture, no fever, no dyspnea, duration of hospitalization, duration of intubation and under ventilation, showed that the difference between these two groups was statistically different (P value < 0.05). In conclusion, inhalation phage therapy may have a potential effect on secondary infection and in the outcome of COVID-19 patients. However, more clinical trials with control confounding factors are needed to further support this concept.

Nanoparticles (NPs) have been widely used in different areas, including consumer products and medicine. In terms of biomedical applications, NPs or NP-based drug formulations have been extensively investigated for cancer diagnostics and therapy in preclinical studies, but the clinical translation rate is low. Therefore, a thorough and comprehensive understanding of the pharmacokinetics of NPs, especially in drug delivery efficiency to the target therapeutic tissue tumor, is important to design more effective nanomedicines and for proper assessment of the safety and risk of NPs. This review article focuses on the pharmacokinetics of both organic and inorganic NPs and their tumor delivery efficiencies, as well as the associated mechanisms involved. We discuss the absorption, distribution, metabolism, and excretion (ADME) processes following different routes of exposure and the mechanisms involved. Many physicochemical properties and experimental factors, including particle type, size, surface charge, zeta potential, surface coating, protein binding, dose, exposure route, species, cancer type, and tumor size can affect NP pharmacokinetics and tumor delivery efficiency. NPs can be absorbed with varying degrees following different exposure routes and mainly accumulate in liver and spleen, but also distribute to other tissues such as heart, lung, kidney and tumor tissues; and subsequently get metabolized and/or excreted mainly through hepatobiliary and renal elimination. Passive and active targeting strategies are the two major mechanisms of tumor delivery, while active targeting tends to have less toxicity and higher delivery efficiency through direct interaction between ligands and receptors. We also discuss challenges and perspectives remaining in the field of pharmacokinetics and tumor delivery efficiency of NPs.

Sorafenib, marketed under the brand name Nexavar, is a multiple tyrosine kinase inhibitor drug that has been actively used in the clinical setting for the treatment of several cancers. However, the low solubility and bioavailability of sorafenib constitute a significant barrier to achieving a good therapeutic outcome. We developed a sorafenib-loaded self-nanoemulsifying drug delivery system (SNEDDS) formulation composed of capmul MCM, tween 80, and tetraglycol, and demonstrated that the SNEDDS formulation could improve drug solubility with excellent self-emulsification ability. Moreover, the sorafenib-loaded SNEDDS exhibited anticancer activity against Hep3B and KB cells, which are the most commonly used hepatocellular carcinoma and oral cancer cell lines, respectively. Subsequently, to improve the storage stability and to increase the possibility of commercialization, a solid SNEDDS for sorafenib was further developed through the spray drying method using Aerosil 200 and PVP K 30. X-ray diffraction and differential scanning calorimeter data showed that the crystallinity of the drug was markedly reduced, and the dissolution rate of the drug was further improved in formulation in simulated gastric and intestinal fluid conditions. study, the bioavailability of the orally administered formulation increases dramatically compared to the free drug. Our results highlight the use of the solid-SNEDDS formulation to enhance sorafenib's bioavailability and outlines potential translational directions for oral drug development.

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), 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. 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, 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.

The compound 3,10-dihydro-1-cyclopenta[]naphtho[2,3-]furan-5,10-dione (IVS320) is a naphthoquinone with antifungal and antichagasic potential, which however has low aqueous solubility. To increase bioavailability, inclusion complexes with β-cyclodextrin (βCD) and methyl-β-cyclodextrin (MβCD) were prepared by physical mixture (PM), kneading (KN) and rotary evaporation (RE), and their -SARS-CoV-2 and antichagasic potential was assessed. The formation of inclusion complexes led to a change in the physicochemical characteristics compared to IVS320 alone as well as a decrease in crystallinity degree that reached 74.44% for the IVS320-MβCD one prepared by RE. The IVS320 and IVS320-MβCD/RE system exhibited -SARS-CoV-2 activity, showing half maximal effective concentrations (EC) of 0.47 and 1.22 μg/mL, respectively. Molecular docking simulation suggested IVS320 ability to interact with the SARS-CoV-2 viral protein. Finally, the highest antichagasic activity, expressed as percentage of growth inhibition, was observed with IVS320-βCD/KN (70%) and IVS320-MβCD/PM (72%), while IVS320 alone exhibited only approximately 48% inhibition at the highest concentration (100 μg/mL).

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.

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.