Specific inter-molecular interaction with sodium glycocholate generates the co-amorphous system showing higher physical stability and aqueous solubility of Y5 receptor antagonist of neuropeptide Y, a brick dust molecule.

Drugs with poor water and lipid solubility are termed "brick dust." We previously successfully developed a co-amorphous system of a novel neuropeptide Y5 receptor antagonist (AntiY5R), a brick dust molecule, using sodium taurocholate (NaTC) as a co-former. However, the maximum improvement in AntiY5R dissolution by the co-amorphous system was only approximately 10 times greater than that of the crystals. Therefore, in the current study, other bile salts, including sodium cholate (NaC), sodium chenodeoxycholate (NaCC), and sodium glycocholate (NaGC), were examined as co-formers to further improve AntiY5R dissolution. NaC, NaCC, and NaGC have glass transition temperatures above 150 °C. All three co-amorphous systems prepared successfully retained the amorphous form of AntiY5R for 3 months at 40 °C, but the co-amorphous system with NaGC (AntiY5R-NaGC; 1:9 M ratio) provided the highest improvement in AntiY5R dissolution, which was approximately 50 times greater than that of the crystals. Possible intermolecular interactions via the glycine moiety of NaGC more than the other bile salts would contribute to the highest dissolution enhancement with AntiY5R-NaGC. Thus, NaGC would be a promising co-former for formulating stable co-amorphous systems to enhance the dissolution behavior of brick dust molecules.

Effect of food on oral pharmacokinetics of edaravone coamorphous dispersion containing bile salts as coformers - Part II.

OBJECTIVES: Edaravone (EDR) is an effective neuroprotective agent in various neurological diseases; however, its use is restricted due to poor oral absorption. Bile salts are known for improving solubility and inhibiting drug crystallization in supersaturated conditions of the gastrointestinal tract (GIT). In our previous work, we prepared coamorphous dispersion (COAM) of EDR with sodium taurocholate (NaTC) using spray drying. The optimized EDR COAM exhibited superior in vitro performance compared to plain EDR. EDR is well absorbed in fasted-over-fed conditions. METHODS: The present work, we conducted a pharmacokinetic study for EDR and EDR COAM in fasted and fed conditions to check effect of food on its oral absorption. The LC-MS/MS-based method was developed and validated to determine the amount of EDR in plasma. RESULTS: The results suggested that EDR COAM did not show a significant difference in Cmax (P=0.3544) and AUC (P=0.1696) of fasted and fed states. On the other hand, plain EDR showed 2-fold and 3-fold reduced Cmax (P<0.0001) and AUC (P=0.0094) in the fed condition, respectively. The Cmax and AUC of EDR COAM were improved in fasted (AUC: 2.56-fold) and fed states (AUC: 5.74-fold) than plain EDR, suggesting better oral absorption of COAM than crystalline EDR without having the effect of food. CONCLUSIONS: The unique structural attributes of NaTC had the potential to inhibit the recrystallization of EDR in GIT, while concurrently reducing the impact of food on the oral absorption of EDR.

Unlocking the potential of flavonoid-based co-crystal and co-amorphous systems.

Flavonoids are polyphenolic compounds that have multiple benefits in treating various life-threatening diseases. Despite their diverse pharmacological activities, the market potential of flavonoids is hampered due to their poor solubility and low bioavailability after oral administration. The current review highlights the role of co-crystals and co-amorphous systems (CAMs) in enhancing the solubility, permeability, bioavailability, and therapeutic efficacy of flavonoids. It also explains the significance of flavonoid-based co-formers in the formation of co-crystals and CAMs with other APIs to improve their efficacy. Future perspectives, patented formulations, commercial medications (including their phases of clinical trials), and challenges associated with the use of flavonoid-based co-crystals and CAMs are also mentioned in the review.

Co-Amorphization of Acemetacin with Basic Amino Acids as Co-Formers for Solubility Improvement and Gastric Ulcer Mitigation.

Acemetacin (ACM) is a new non-steroidal anti-inflammatory drug with anti-inflammatory, analgesic, and antipyretic effects. However, the poor water solubility and gastrointestinal side effects limit its use. Recently, the co-amorphous (CAM) strategy has attracted great interest to improve solubility for poorly water-soluble drugs, and basic amino acids have the potential to protect the gastrointestinal tract. In order to develop a highly efficient and low-toxic ACM formulation, we prepared ACM CAM systems, with basic amino acids (lysine, arginine, and histidine) as co-formers, using a cryo-milling method. The solid-state behaviors of the ACM CAM systems were characterized by polarizing light microscopy, differential scanning calorimetry, and powder X-ray diffraction. Fourier transform infrared spectroscopy and molecular docking were carried out to understand the formation mechanism. Moreover, the gastro-protective effects of ACM CAM systems were evaluated in a rat gastric ulcer model. The results demonstrated that the CAM systems improved the dissolution rates of ACM compared with the neat amorphous counterpart. Furthermore, ACM CAM systems are significantly effective in mitigating the ACM-induced gastric ulcer in rats, and the ulcer inhibition rates were almost 90%. More importantly, this study provided a useful method for mitigating drug-induced gastrointestinal damage and broadened the applications of drug-amino acid CAM systems.

Nucleotides as new co-formers in co-amorphous systems: Enhanced dissolution rate, water solubility and physical stability.

Developing co-amorphous systems is an attractive strategy to improve the dissolution rate of poorly water-soluble drugs. Various co-formers have been investigated. However, previous studies revealed that it is a challenge to develop satisfied acidic co-formers, e.g., acidic amino acids showed much poorer co-former properties than neutral and basic amino acids. Only a few acidic co-formers have been reported, such as aspartic acid, glutamic acid, and some other organic acids. Thus, this study aims to explore the possibility of adenosine monophosphate and adenosine diphosphate used as acidic co-formers. Mebendazole, celecoxib and tadalafil were used as the model drugs. The drug-co-former co-amorphous systems were prepared via ball milling and confirmed using XRPD. The dissolution study suggested that the solubility and dissolution rate of the drug-co-formers systems were increased significantly compared to the corresponding crystalline and amorphous drugs. The stability study revealed that using the two nucleotides as co-formers enhanced the physical stability of pure amorphous drugs. Molecular interactions were observed in MEB-co-former and TAD-co-former systems and positively affected the pharmaceutical performance of the investigated co-amorphous systems. In conclusion, the two nucleotides could be promising potential acidic co-formers for co-amorphous systems.

Effects of Polymers on Cocrystal Growth in a Drug-Drug Coamorphous System: Relations between Glass-to-Crystal Growth and Surface-Enhanced Crystal Growth.

Coamorphous and cocrystal drug delivery systems provide attractive crystal engineering strategies for improving the solubilities, dissolution rates, and oral bioavailabilities of poorly water-soluble drugs. Polymeric additives have often been used to inhibit the unwanted crystallization of amorphous drugs. However, the transformation of a coamorphous phase to a cocrystal phase in the presence of polymers has not been fully elucidated. Herein, we investigated the effects of low concentrations of the polymeric excipients poly(ethylene oxide) (PEO) and poly(vinylpyrrolidone) (PVP) on the growth of carbamazepine-celecoxib (CBZ-CEL) cocrystals from the corresponding coamorphous phase. PEO accelerated the growth rate of the cocrystals by increasing the molecular mobility of the coamorphous system, while PVP had the opposite effect. The coamorphous CBZ-CEL system exhibited two anomalously fast crystal growth modes: glass-to-crystal (GC) growth in the bulk and accelerated crystal growth at the free surface. These two fast growth modes both disappeared after doping with PEO (1-3% w/w) but were retained in the presence of PVP, indicating a potential correlation between the two fast crystal growth modes. We propose that the different effects of PEO and PVP on the crystal growth modes arose from weaker effects of the polymers on cocrystallization at the surface than in the bulk. This work provides a deep understanding of the mechanisms by which polymers influence the cocrystallization kinetics of a multicomponent amorphous phase and highlights the importance of polymer selection in stabilizing coamorphous systems or preparing cocrystals via solid-based methods.

Combination of co-amorphization with SNEDDS outperforms Ofev® in the oral absorption of nintedanib.

Nintedanib (NTD), approved for the treatment of idiopathic pulmonary fibrosis and advanced non-small cell lung cancer, is one of brick dusts with high melting point. Although NTD has been marketed as Ofev®, a soft capsule of NTD ethanesulfonate (NTD-ESA) suspended in oil components, the oral bioavailability is quite low and highly variable. To improve the oral absorption behavior of NTD, we prepared SNEDDS formulation containing NTD-(+)-10-camphorsulfonic acid (CSA) complex with 2% HPMCP-50. CSA disrupted the high crystallinity of NTD-ESA and the formed complex, NTD-CSA, was found to be amorphous by DSC and XRPD. NTD-CSA provided solubilities in various vehicles much higher than NTD-ESA. Under the gastric luminal condition, NTD-CSA SNEDDS with or without 2% HPMCP-50 and NTD-CSA powder indicated very good dissolution of NTD from early time periods, while NTD was gradually dissolved until around 60 min from NTD-ESA and Ofev®. Under the small intestinal luminal condition, in contrast, both NTD-CSA SNEDDS formulations almost completely dissolved NTD throughout the experiments, while Ofev®, NTD-CSA, and NTD-ESA exhibited a very poor dissolution of NTD. In the in vivo absorption study, NTD-CSA SNEDDS with 2% HPMCP-50 significantly improved NTD absorption and reduced the inter-individual variation in oral absorption behavior compared with Ofev®.

Insight into Formation, Synchronized Release and Stability of Co-Amorphous Curcumin-Piperine by Integrating Experimental-Modeling Techniques.

Intermolecular interactions between drug and co-former are crucial in the formation, release and physical stability of co-amorphous system. However, the interactions remain difficult to investigate with only experimental tools. In this study, intermolecular interactions of co-amorphous curcumin-piperine (i.e., CUR-PIP CM) during formation, dissolution and storage were explored by integrating experimental and modeling techniques. The formed CUR-PIP CM exhibited the strong hydrogen bond interaction between the phenolic OH group of CUR and the CO group of PIP as confirmed by FTIR, ss 13C NMR and molecular dynamics (MD) simulation. In comparison to crystalline CUR, crystalline PIP and their physical mixture, CUR-PIP CM performed significantly increased dissolution accompanied by the synchronized release of CUR and PIP, which arose from the greater interaction energy of H2O-CUR molecules and H2O-PIP molecules than CUR-PIP molecules, breaking the hydrogen bond between CUR and PIP molecules, and then causing a pair-wise solvation of CUR-PIP CM at the molecular level. Furthermore, the stronger intermolecular interaction between CUR and PIP was revealed by higher binding energy of CUR-PIP molecules, which contributed to the excellent physical stability of CUR-PIP CM over amorphous CUR or PIP. The study provides a unique insight into the formation, release and stability of co-amorphous system from MD perspective. Meanwhile, this integrated technique can be used as a practical methodology for the future design of co-amorphous formulations.

Improved Dissolution Properties of Co-amorphous Probucol with Atorvastatin Calcium Trihydrate Prepared by Spray-Drying.

A co-amorphous model drug was prepared by the spray-drying (SD) of probucol (PC) and atorvastatin calcium trihydrate salt (ATO) as low water solubility and co-former components, respectively. The physicochemical properties of the prepared samples were characterized by powder X-ray diffraction (PXRD) analysis, thermal analysis, Fourier transform infrared spectroscopy (FTIR), and dissolution tests. Stability tests were also conducted under a stress environment of 40 °C and 75% relative humidity. The results of PXRD measurements and thermal analysis suggested that PC and ATO form a co-amorphous system by SD. Thermal analysis also indicated an endothermic peak that followed an exotherm in amorphous PC and a physical mixture (PM) of amorphous PC and ATO; however, no endothermic peak was detected in the co-amorphous system. The dissolution profiles for PC in the co-amorphous sample composed of PC and ATO were improved compared to those for raw PC crystals or the PM. Stability tests indicated that the co-amorphous material formed by PC and ATO can be stored for 35 d without crystallization, whereas amorphous PC became crystallized within a day. Therefore, co-amorphization of PC and ATO prepared by SD is considered to be a useful method to improve the solubility of PC in water.

Preparation and Characterization of a Rifampicin Coamorphous Material with Tromethamine Coformer: An Experimental-Theoretical Study.

Rifampicin (RIF) is an antibiotic used to treat tuberculosis and leprosy. Even though RIF is a market-available drug, it has a low aqueous solubility, hindering its bioavailability. Among the strategies for bioavailability improvement of poorly soluble drugs, coamorphous systems have been revealed as an alternative in the increase of the aqueous solubility of drug systems and at the same time also increasing the amorphous state stability and dissolution rate when compared with the neat drug. In this work, a new coamorphous form from RIF and tromethamine (TRIS) was synthesized by slow evaporation. Structural, electronic, and thermodynamic properties and solvation effects, as well as drug-coformer intermolecular interactions, were studied through density functional theory (DFT) calculations. Powder X-ray diffraction (PXRD) data allowed us to verify the formation of a new coamorphous. In addition, the DFT study indicates a possible intermolecular interaction by hydrogen bonds between the available amino and carbonyl groups of RIF and the hydroxyl and amino groups of TRIS. The theoretical spectra obtained are in good agreement with the experimental data, suggesting the main interactions occurring in the formation of the coamorphous system. PXRD was used to study the physical stability of the coamorphous system under accelerated ICH conditions (40 °C and 75% RH), indicating that the material remained in an amorphous state up to 180 days. The thermogravimetry result of this material showed a good thermal stability up to 153 °C, and differential scanning calorimetry showed that the glass temperature (Tg) was at 70.0 °C. Solubility studies demonstrated an increase in the solubility of RIF by 5.5-fold when compared with its crystalline counterpart. Therefore, this new material presents critical parameters that can be considered in the development of new coamorphous formulations.

Monophasic coamorphous sulpiride: a leap in physicochemical attributes and dual inhibition of GlyT1 and P-glycoprotein, supported by experimental and computational insights.

Study aimed to design and development of a supramolecular formulation of sulpiride (SUL) to enhance its solubility, dissolution and permeability by targeting a novel GlyT1 inhibition mechanism. SUL is commonly used to treat gastric and duodenal ulcers, migraine, anti-emetic, anti-depressive and anti-dyspeptic conditions. Additionally, Naringin (NARI) was incorporated as a co-former to enhance the drug's intestinal permeability by targeting P-glycoprotein (P-gp) efflux inhibition. NARI, a flavonoid has diverse biological activities, including anti-apoptotic, anti-oxidant, and anti-inflammatory properties. This study aims to design and develop a supramolecular formulation of SUL with NARI to enhance its solubility, dissolution, and permeability by targeting a novel GlyT1 inhibition mechanism, extensive experimental characterization was performed using solid-state experimental techniques in conjunction with a computational approach. This approach included quantum mechanics-based molecular dynamics (MD) simulation and density functional theory (DFT) studies to investigate intermolecular interactions, phase transformation and various electronic structure-based properties. The findings of the miscibility study, radial distribution function (RDF) analysis, quantitative simulations of hydrogen/π-π bond interactions and geometry optimization aided in comprehending the coamorphization aspects of SUL-NARI Supramolecular systems. Molecular docking and MD simulation were performed for detailed binding affinity assessment and target validation. The solubility, dissolution and ex-vivo permeability studies demonstrated significant improvements with 31.88-fold, 9.13-fold and 1.83-fold increments, respectively. Furthermore, biological assessments revealed superior neuroprotective effects in the SUL-NARI coamorphous system compared to pure SUL. In conclusion, this study highlights the advantages of a drug-nutraceutical supramolecular formulation for improving the solubility and permeability of SUL, targeting novel schizophrenia treatment approaches through combined computational and experimental analyses.Communicated by Ramaswamy H. Sarma.

Indomethacin-omeprazole as therapeutic hybrids? Salt and co-amorphous systems enhancing physicochemical and pharmacological properties.

Multidrug therapeutic hybrids constitute a promising proposal to overcome problems associated with traditional formulations containing physical mixtures of drugs, potentially improving pharmacological and pharmaceutical performance. Indomethacin (IND) is a non-selective non-steroidal anti-inflammatory drug (NSAIDs) that acts by inhibiting normal processes of homeostasis, causing a series of side effects, such as gastrointestinal symptoms. Proton pump inhibitors, such as omeprazole (OME), have been used to treat such gastrointestinal tract symptoms. In this work, two new multidrug therapeutic hybrids were prepared (an IND:OME salt and an IND:OME co-amorphous system) by ball mill grinding crystalline IND and OME under different conditions, i.e., liquid assisted grinding (LAG) with ethanol and dry grinding, respectively. The crystalline salt returned to a neutral state co-amorphous system when submitted to ball mill grinding in the absence of solvent (dry grinding), but the reverse process (LAG of the IND:OME co-amorphous system) showed partial decomposition of OME. The IND:OME co-amorphous system showed a higher physical stability than the neat IND and OME amorphous materials (with an amorphous stability longer than 100 days, compared to 4 and 16 h for the neat amorphous drugs, respectively, when stored at dry conditions at room temperature). Furthermore, OME presented a higher chemical stability in solution when dissolved from a salt form than from the pure crystalline form. The dissolution studies showed a dissolution enhancement for IND in both salt (1.8-fold after 8 h of dissolution) and co-amorphous (2.5-fold after 8 h of dissolution) forms. Anti-inflammatory activity using a mice paw oedema model showed an increase of the pharmacological response to IND at a lower dose (∼5mg/kg) for both IND:OME salt (2.8-fold) and IND:OME co-amorphous system (3.2-fold) after 6 h, when compared to the positive control group (IND, administered at 10 mg/kg). Additionally, the anti-inflammatory activity of both salt and co-amorphous form was faster than for the crystalline IND. Finally, an indomethacin-induced gastric ulceration assay in mice resulted in a higher mucosal protection at the same dose (40 mg/kg) for both IND:OME salt and IND:OME co-amorphous system when compared with crystalline OME.

Molecular interactions of hydrated co-amorphous systems of prilocaine and lidocaine.

It is generally accepted that water as a plasticizer can decrease the glass transition temperatures (Tgs) of amorphous drugs and drug excipient systems. However, previous studies suggest that water, as an anti-plasticizer, can increase the Tgs of co-amorphous systems of prilocaine (PRL) and lidocaine (LID). In order to investigate the intermolecular interactions between water and co-amorphous PRL-LID systems, Fourier transform infrared spectroscopy (FTIR) and principal component analysis (PCA) were conducted. Water was found to bind with the carbonyl groups of PRL and LID molecularly evenly in the hydrated co-amorphous PRL-LID systems. Quantum chemical simulations visually confirmed the interactions between water and co-amorphous PRL-LID systems. Furthermore, the physical stability of hydrated co-amorphous PRL-LID systems was improved due to the anti-plasticizing effect of water, compared with the anhydrous samples. The preference of water to interact with the carbonyl groups of PRL and LID as binding sites could be associated with the anti-plasticizing effect of water on the co-amorphous PRL-LID systems.

Development and characterization of co-amorphous griseofulvin/L-leucin by modified solvent processing hot-melt extrusion.

Co-amorphous systems (CAMS) were developed between griseofulvin (GRI) and L-leucine (LEU) at 2:1 wt ratio, by application of a novel solvent assisted hot-melt extrusion (HME) method that involved wet processing/drying of the feeds prior to extrusion. CAMS formation was confirmed by powder crystallography (pXRD) and thermal analysis (DSC). Intermolecular H-bonding between the carbonyl groups of GRI and the hydroxyl and amino groups of LEU were identified by vibrational spectroscopy (ATR-FTIR). The measured glass transition temperatures (Tg) of the extrudates from feeds processed with aqueous acetic acid (AcOH) were markedly lower than that of neat amorphous GRI and values predicted from Gordon-Taylor equation, indicating plasticizing action of AcOH. Drug concentrations during dissolution of CAMS under non-sink conditions (Sink Index 0.0115) were up to x82 higher at plateau compared to crystalline drug solubility. The degree of supersaturation lasted for at least 24 h. Plasticizer (Compritol®/Kolliphor® 75/25) added before extrusion did not impact significantly on CAMS formation but altered the dissolution profile from a spring-and-parachute profile to gradual rise to maximum. These findings reinforce the application of drug/amino acid-based CAMS in formulation, particularly for high-dose drugs, for which polymers are unsuited due to the required large proportions.

Drug-Coformer Loaded-Mesoporous Silica Nanoparticles: A Review of the Preparation, Characterization, and Mechanism of Drug Release.

Drug-coformer systems, such as coamorphous and cocrystal, are gaining recognition as highly effective strategies for enhancing the stability, solubility, and dissolution of drugs. These systems depend on the interactions between drug and coformer to prevent the conversion of amorphous drugs into the crystalline form and improve the solubility. Furthermore, mesoporous silica (MPS) is also a promising carrier commonly used for stabilization, leading to solubility improvement of poorly water-soluble drugs. The surface interaction of drug-MPS and the nanoconfinement effect prevent amorphous drugs from crystallizing. A novel method has been developed recently, which entails the loading of drug-coformer into MPS to improve the solubility, dissolution, and physical stability of the amorphous drug. This method uses the synergistic effects of drug-coformer interactions and the nanoconfinement effect within MPS. Several studies have reported successful incorporation of drug-coformer into MPS, indicating the potential for significant improvement in dissolution characteristics and physical stability of the drug. Therefore, this study aimed to discuss the preparation and characterization of drug-coformer within MPS, particularly the interaction in the nanoconfinement, as well as the impact on drug release and physical stability.

Drug-drug co-amorphous systems: An emerging formulation strategy for poorly water-soluble drugs.

Overcoming the poor water solubility of small-molecule drugs is a major challenge in the development of clinical pharmaceuticals. Amorphization of crystalline drugs is a highly effective strategy to improve their aqueous solubility. However, amorphous drugs are thermodynamically unstable and likely to crystallize during manufacturing and storage. Recently, drug-drug co-amorphous systems have emerged as a novel strategy to not only enable enhanced dissolution and physical stability of the individual drugs within the system but also to provide a strategy for combination therapy of the same or different clinical indications. This review serves to highlight advances in the methods used to manufacture and characterize drug-drug co-amorphous systems, summarize drug-drug co-amorphous applications reported in recent decades, and provide an outlook on future possibilities and perspectives.

Development and characterization of a spray-dried inhalable ternary combination for the treatment of Pseudomonas aeruginosa biofilm infection in cystic fibrosis.

Cystic fibrosis (CF) is an inherited lung disease characterised by the accumulation of thick layers of dried mucus in the lungs which serve as a nidus for chronic infection. Pseudomonas aeruginosa is the predominant cause of chronic lung infection in cystic fibrosis. The dense mucus coupled with biofilm formation hinder antibiotic penetration and prevent them from reaching their target. Mucoactive agents are recommended in the treatment of CF in combination with antibiotics. In spite of the extensive research in developing novel drug combinations for the treatment of lung infection in CF, to our knowledge, there is no study that combines antibiotic, antibiofilm and mucoactive agent in a single inhaled dry powder formulation. In the present study, we investigate the possibility of adding a mucoactive agent to our previously developed ciprofloxacinquercetin (antibiotic-antibiofilm) dry powder for inhalation. Three mucoactive agents, namely mannitol (MAN), N-acetyl-L-cysteine (NAC) and ambroxol hydrochloride (AMB), were investigated for this purpose. The ternary combinations were prepared via spray drying without the addition of excipients. All ternary combinations conserved or improved the antibacterial and biofilm inhibition activities of ciprofloxacin against P. aeruginosa (ATCC 10145). The addition of AMB resulted in an amorphous ternary combination (SD-CQA) with superior physical stability as indicated by DSC and nonambient XRPD. Furthermore, SD-CQA displayed better in vitro aerosolization performance (ED ∼ 71 %; FPF ∼ 49 %) compared to formulations containing MAN and NAC (ED ∼ 64 % and 44 %; FPF ∼ 44 % and 29 %, respectively). In conclusion, a ternary drug combination powder with suitable aerosolization, physical stability and antibacterial/antibiofilm properties was prepared by a single spray drying step.

Recent advances in dual-drug co-amorphous systems.

Poor solubility of drugs and therapeutic candidates poses a significant challenge in drug research and development. Biopharmaceutical class II drugs exhibit limited absorption because of their weak solubility and high permeability. Co-amorphous systems (CAMs) have been studied widely as a way to improve the solubility of drugs. This review summarizes recent advancements in dual-drug CAMs, including improvements in formulation, manufacturing, and solid-state characterization, and highlights the importance of enhancing solubility and stability. It emphasizes the potential synergistic effects of two drugs in CAMs and explores formulation strategies and challenges related to maintaining the amorphous state. Case studies demonstrate the successful application of CAMs in combination therapies that offer improved therapeutic efficacy.

New Perspectives for Antihypertensive Sartans as Components of Co-crystals and Co-amorphous Solids with Improved Properties and Multipurpose Activity.

Sartans (angiotensin II receptor blockers, ARBs), drugs used in the treatment of hypertension, play a principal role in addressing the global health challenge of hypertension. In the past three years, their potential use has expanded to include the possibility of their application in the treatment of COVID-19 and neurodegenerative diseases (80 clinical studies worldwide). However, their therapeutic efficacy is limited by their poor solubility and bioavailability, prompting the need for innovative approaches to improve their pharmaceutical properties. This review discusses methods of co-crystallization and co-amorphization of sartans with nonpolymeric, low molecular, and stabilizing co-formers, as a promising strategy to synthesize new multipurpose drugs with enhanced pharmaceutical properties. The solid-state forms have demonstrated the potential to address the poor solubility limitations of conventional sartan formulations and offer new opportunities to develop dual-active drugs with broader therapeutic applications. The review includes an in-depth analysis of the co-crystal and co-amorphous forms of sartans, including their properties, possible applications, and the impact of synthetic methods on their pharmacokinetic properties. By shedding light on the solid forms of sartans, this article provides valuable insights into their potential as improved drug formulations. Moreover, this review may serve as a valuable resource for designing similar solid forms of sartans and other drugs, fostering further advances in pharmaceutical research and drug development.

Amorphization of Low Soluble Drug with Amino Acids to Improve Its Therapeutic Efficacy: a State-of-Art-Review.

Low aqueous solubility of drug candidates is an ongoing challenge and pharmaceutical manufacturers pay close attention to amorphization (AMORP) technology to improve the solubility of drugs that dissolve poorly. Amorphous drug typically exhibits much higher apparent solubility than their crystalline form due to high energy state that enable them to produce a supersaturated state in the gastrointestinal tract and thereby improve bioavailability. The stability and augmented solubility in co-amorphous (COA) formulations is influenced by molecular interactions. COA are excellent carriers-based drug delivery systems for biopharmaceutical classification system (BCS) class II and class IV drugs. The three important critical quality attributes, such as co-formability, physical stability, and dissolution performance, are necessary to illustrate the COA systems. New amorphous-stabilized carriers-based fabrication techniques that improve drug loading and degree of AMORP have been the focus of emerging AMORP technology. Numerous low-molecular-weight compounds, particularly amino acids such as glutamic acid, arginine, isoleucine, leucine, valine, alanine, glycine, etc., have been employed as potential co-formers. The review focus on the prevailing drug AMORP strategies used in pharmaceutical research, including in situ AMORP, COA systems, and mesoporous particle-based methods. Moreover, brief characterization techniques and the application of the different amino acids in stabilization and solubility improvements have been related.