Aqueous Solubility Of Drug Research Articles

Fabrication of β-cyclodextrin-based microgels for enhancing solubility of Terbinafine: An in-vitro and in-vivo toxicological evaluation

Abstract Solubility enhancement of poorly aqueous-soluble drugs, like Terbinafine (TBN), is a critical challenge in formulating effective dosage forms. This study focused on developing β-cyclodextrin (β-CD) and polyacrylamide (PAM)-based microgels to address the solubility issue of TBN, classified as a biopharmaceutics classification system class II drug. The microgels were crafted through free radical polymerization, employing methylene bisacylamide as a cross-linker and methacrylic acid as a monomer, initiated by ammonium persulfate. Comprehensive characterizations, including Fourier transform infrared, thermo-gravimetric analysis, differential scanning calorimetry, scanning electron microscopy, powder X-ray diffractometry analysis, Zeta size, and Zeta potential, were conducted. In vitro studies, such as drug release and swelling, were performed at pH 1.2. Toxicity analysis in rabbits revealed zero toxicity. These β-CD/PAM microgels successfully enhanced the solubility of TBN.

Mechanisms of drug release from a melt-milled, poorly soluble drug substance

Increasing the dissolution kinetics of low aqueous soluble drugs is one of the main priorities in drug formulation. New strategies must be developed, which should consider the two main dissolution mechanisms: surface reaction and diffusion.One promising tool is the so-called solid crystal suspension, a solid dispersion consisting of purely crystalline substances. In this concept, reducing the drug particle size and embedding the particles in a hydrophilic excipient increases the dissolution kinetics. Therefore, a solid crystal suspension containing submicron drug particles was produced via a modified stirred media milling process. A geometrical phase-field approach was used to model the dissolution behavior of the drug particles.A carrier material, xylitol, and the model drug substance, griseofulvin, were ground in a pearl mill. The in-vitro dissolution profile of the product was modeled to gain a deep physical understanding of the dissolution process. The used numerical tool has the potential to be a valuable approach for predicting the dissolution behavior of newly developed formulation strategies.

Multichannel 3D-printed bionanoparticles-loaded tablet (M3DPBT): designing, development, and in vitro functionality assessment

BackgroundThe intersubject variability which was related to the genetic makeup was the major cause of change in pharmacological and pharmacokinetic behavior of same dosage form in varied human being. 3D printing technology will help therapy evolve and eliminate the limitations of conventional technologies. Nebivolol's (NBL)-limited oral bioavailability is mainly due to its poor aqueous solubility. The research aims to combine advanced 3D printing technology and nanotechnology to design customized therapy and enhance the functionality of NBL using a statistical approach.Results and discussionThe results of the phase solubility indicated that NBL was a poorly aqueous soluble drug. Its solubility was increased by employing nanoparticle drug delivery, which is a promising solubility enhancement technique. The 32 full factorial design was employed to develop and optimize bionanoparticles (BNPs) by solvent evaporation technique using poly (lactic-co-glycolic acid 50:50) (PLGA 50:50) and poloxamer-407 as a surfactant. The BNPs were characterized by % encapsulation efficiency (% EE), Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimeter (DSC), transmission electron microscope (TEM), zeta potential, polydispersity index (PDI), particle size, in vitro drug release, etc. The BNPs loaded of NBL were further incorporated into the multichannel 3D-controlled release tablets made by PVA filaments employing fused deposition modeling (FDM) technology optimized by central composite design (CCD). Multichannel 3D-printed bionanoparticles-loaded tablet (M3DPBT) was optimized using CCD. All designed M3DPBTs were evaluated for post-fabrication parameters. The optimized M3DPBT could release more than 85% NBL within 10 h.ConclusionsThe newly fabricated M3DPBT was found stable. The amount of PLGA 50:50 and Polaxomer was significant for developing BNPs. % infill and layer height were observed as critical for the designing M3DPBT. The combined novel 3D printing and nanotechnology technology will open a new direction for patient compliance and better therapeutic effects.Graphical abstractDesigning and developing of M3DPBT is substantially improve the patient compliance and therapeutic effectiveness of Nebivolol.

Study on co-amorphous emerging solubilization behavior after gelation during dissolution: The importance of complexation and anti-crystallization

Co-amorphous (CM) is a promising technology for enhancing the aqueous solubility of insoluble drugs, but the gelation phenomenon has often occurred during the dissolution process and seriously threatened their solubility/dissolution performance. Therefore, it’s quite important to design favorable CM systems to alleviate or even avoid the adverse effects of gelation phenomenon. In this study, CM systems of taxifolin (TAX) and oxymatrine (OMT) (TAX-OMT CMs) were constructed to improve the solubility and dissolution properties of TAX. Interestingly, TAX-OMT CMs gradually aggregated and obviously gelled during dissolution, but the solubility and dissolution of TAX in TAX-OMT CMs were significantly enhanced compared to crystalline TAX. Consequently, the underlying solubilization mechanisms of TAX-OMT CMs after gelation were systematically explored. For one thing, the complexation between the two components in TAX-OMT CMs was verified by phase solubility, fluorescence spectroscopy and isothermal titration calorimetry. For another, the residual solids of TAX-OMT CMs after dissolution evaluation were thoroughly characterized by means of powder X-ray diffraction, fourier transform infrared spectroscopy, scanning electron microscopy, which showed the anti-crystallization property of TAX-OMT CMs. Furthermore, molecular simulation demonstrated the intermolecular interactions of TAX-OMT CMs alone and TAX-OMT complexes in aqueous solution. Finally, pharmacokinetics study in rats suggested that the bioavailability of TAX in TAX-OMT CM (1:2) was approximately 5.5-fold higher than that of crystalline TAX after oral administration. Collectively, this study reveals the importance of complexation and anti-crystallization effects of CM systems on maintaining solubilization behavior after gelation, providing an effective strategy to improve the absorption performance of pharmaceutical CM systems.

New Horizons in Antiretroviral Drug Delivery Systems for HIV Management.

Human Immunodeficiency Virus (HIV) infection is still a major global problem, whose drug treatment consists of prophylactic prevention and antiretroviral combination therapy for better pharmacological efficacy and control of circulating virus. However, there are still pharmacological problems that need to be overcome, such as low aqueous solubility of drugs, toxicity, and low patient adherence. Drug delivery technologies can be used to overcome these barriers. This review summarized the latest drug delivery systems for HIV treatment. Initially, an overview of the current therapy was presented along with the problems it presents. Then, the latest drug delivery systems used to overcome the challenges imposed in conventional HIV therapy were discussed. Articles published in the last 10 years were reviewed to obtain information on the innovations brought to HIV treatment. Delivery systems can improve the physicochemical properties of antiretroviral drugs, causing greater aqueous solubility, stability, and cellular and membrane permeability, which was reflected in the greater bioavailability of these drugs. However, more stability studies and techniques development are still needed to allow industrial scaling for large-scale production of drugs that use these technologies.

Reactivities of 4-amino salicylic acid and its ‘Green’ inhibition into nano sized β-cyclodextrin for Anti-Tuberculosis drug delivery

In the present work, 4-amino salicylic acid (PAS) which is an oral antibiotic against tuberculosis is being investigated for its potential “Green” effectivity in trapped conditions within nano sized good solubilizing drug receptor. The process is totally “green” as no toxic materials, chemicals and solvent other than water has been used throughout the encapsulation /complexation process. Cyclodextrin glycosyltransferase (3CGT) and its by-product beta (β)-cyclodextrin (β-CD) usually act as nano sized good solubilizing agents for many drugs. In aqueous medium both 3CGT and β-CD can create drug: receptor complex by encapsulating the drug into its nano sized cavity and can increase the aqueous solubility of probe drug depending on the ionic strength. PAS was initially screened by its drug likeness properties by ADMET analysis. Structural analysis and chemical reactivity of PAS have been checked by density functional theory with basis set B3LYP/6-311G++*(d,p) in aqueous environment. The electronic properties (atomic charges, electrostatic potential, and uv–visible absorption & fluorescence analysis) have been studied to check the possibility of 1:1 complex formation between PAS: β-CD. To understand the type and strength of interactions between PAS and receptor, molecular docking and molecular dynamics simulations have been performed between PAS and cyclodextrin glycosyltransferase (3GGT). PAS has shown strong interaction possibilities both as 1:1 inclusion complex (PAS: β-CD) and as PAS: 3CGT complex. Our in-silico and experimental outcomes have recommended 4-amino salicylic acid’s better efficacy as a promising inhibitor inside cyclodextrin nano-cavity for targeting tuberculosis.

Designing of fucosylated dendrimers as a biocompatible carrier for the targeted delivery of chrysin to human lung cancer cells

Dendrimers, a polymeric macromolecule, have been explored for improving the solubility of water-insoluble drugs, and PAMAM is the most explored dendrimer in nanomedicine. But amine-terminated PAMAM dendrimers confer toxicity to healthy cells. Chrysin (CRY) is a plant-derived phenolic component with anticancer properties and has emerged as a safer drug for the treatment of various cancers, including lung cancer. However, its limited aqueous solubility and poor in vivo stability are the major hurdles to its development as a potential anticancer molecule. In the present work, generation 4 PAMAM dendrimers were functionalized with fucose to overcome the toxicity of dendrimers, enhance the aqueous solubility of CRY, and improve drug targeting to cancer cells. The prepared CRY-loaded fucosylated PAMAM dendrimers (CRY-FUC-PAMAM) were found to have high aqueous solubility and sustained drug release. In the in-vitro studies, CRY-FUC-PAMAM showed improved cytotoxicity with a lower IC50 value at both 24 h and 48 h (1.8 μg/mL and 0.7 μg/mL, respectively), resulting from increased apoptosis and cellular uptake of FUC-PAMAM in A549 human lung cancer cells in comparison to free CRY, whereas FUC-PAMAM was found to be non-toxic. Overall, this biocompatible fucosylated dendrimer could be used as a nanocarrier for the delivery of CRY as a targeted nanomedicine for lung cancer.

QbD-Based Development and Evaluation of Pazopanib Hydrochloride Extrudates Prepared by Hot-Melt Extrusion Technique: In Vitro and In Vivo Evaluation.

Pazopanib hydrochloride (PZB) is a protein kinase inhibitor approved by the United States Food and Drug Administration and European agencies for the treatment of renal cell carcinoma and other renal malignancies. However, it exhibits poor aqueous solubility and inconsistent oral drug absorption. In this regard, the current research work entails the development and evaluation of the extrudates of pazopanib hydrochloride by the hot-melt extrusion (HME) technique for solubility enhancement and augmenting oral bioavailability. Solid dispersion of the drug was prepared using polymers such as Kollidon VA64, hydroxypropylmethylcellulose (HPMC), Eudragit EPO, and Affinisol 15LV in a 1:2 ratio by the HME process through a lab-scale 18 mm extruder. Systematic optimization of the formulation variables was carried out with the help of custom screening design (JMP Software by SAS, Version 14.0) to study the impact of polymer type and plasticizer level on the quality of extrudate processability by measuring the torque value, appearance, and disintegration time as the responses. The polymer blends containing Kollidon VA64 and Affinisol 15LV resulted in respective clear transparent extrudates, while Eudragit EPO and HPMC extrudates were found to be opaque white and brownish, respectively. Furthermore, evaluation of the impact of process parameters such as screw rpm and barrel temperature was measured using a definitive screening design on the extrude appearance, torque, disintegration time, and dissolution profile. Based on the statistical outcomes, it can be concluded that barrel temperature has a significant impact on torque, disintegration time, and dissolution at 30 min, while screw speed has an insignificant impact on the response variables. Affinisol extrudates showed less moisture uptake and faster dissolution in comparison to Kollidon VA64 extrudates. Affinisol extrudates were evaluated for polymorphic stability up to a 3-month accelerated condition and found no recrystallization. PZB-Extrudates using the Affinisol polymer (Test formulation A) revealed significantly higher bioavailability (AUC) in comparison to the free Pazopanib drug and marketed formulation.

Effect of Tween and CTAB surfactants on aqueous solubility of the silibinin anticancer drug studied by using physicochemical properties at 310.15 K

The silibinin (SB) is an anticancer drug exhibits partial solubility in aqueous medium due to its slightly hydrophobic nature. In this context, the aqueous solubility of SB with Tween 40 (Tw 40), Tween 60 (Tw 60), Tween 80 (Tw 80) and Cetyltrimethylammonium bromide (CTAB) surfactants at 310.15 K are reported. The physicochemical properties (PCPs) such as density (ρ, g cm−3), Apparent Molar Volume (Vϕ, cm3·mol−1), viscosity (η, mPa.s), surface tension (γ, mNm−1), friccohesity (σ, s.m−1), activation energy (Δµ2*, kJ/mol), and molecular radii (r, nm) of SB with aqueous solution of Tw 40, Tw 60, Tw 80 and CTAB surfactants separately. The PCPs reflects the state of intermolecular forces (IMF) developed between SB and aqueous solutions of Tween (40, 60, 80) and CTAB surfactants with concentration varied from 25 to 150 µM (µM). This study focused on intermolecular interacting mechanism determined by using PCPs to evaluate self-aggregation potential of SB in aqueous surfactants solution. The PCPs data furnished interaction and structure breaking behavior of SB with surfactant molecules. The development of hydrogen bond (HB), hydrophilic, hydrophobic and electrostatic interactions of SB with surfactants which revealed that the structure dependent interacting activities enhances with increasing concentration of SB in aqueous surfactants.

Improved Dissolution and Solubility Characteristics of Clopidogrel Bisulphate using Gelucire 44/14

Clopidogrel bisulphate is a poorly aqueous soluble drug belonging to BCS Class II. The drug is widely used to treat blood clotting in patients with peripheral, coronary, and cerebrovascular disorders, but its low bioavailability raises concern. The present study involves an effort for enhancing the solubility and drug release by transforming the drug into solid dispersions. The solid dispersions of clopidogrel bisulphate were prepared with Gelucire 44/14 using solvent evaporation method. The prepared physical mixture and solid dispersions were characterized for drug-carrier interaction, drug content, solubility, and dissolution rate. Results confirmed the increase in drug solubility with increasing polymer concentration. The dissolution profile was found to substantially improve from solid dispersion with maximum drug release in the ratio of 1:5 on comparing it with pure drug and physical mixture. FT‐IR spectra of selected solid dispersion revealed no chemical interaction between drug and polymers while the presence of the drug in the amorphous state was confirmed by DSC thermograms and X-ray diffraction, indicating better dissolution characteristics. The solid dispersions were also found to be stable under accelerated stability conditions. Keywords: Clopidogrel bisulphate, Bioavailability, Solid dispersions, Gelucire 44/14, Solubility Enhancement

Advances in Nanocarriers for Delivering Therapeutic Agents Against Hepatitis B Virus

Hepatitis B virus (HBV) infection is a crucial public health issue and a major cause of liver disease, such as cirrhosis and hepatocellular carcinoma. At present, orally administered small molecule drugs, such as nucleoside / nucleotide analogues, are recommended as the first‐line treatment for HBV. However, the therapeutic efficacy of these drugs is hindered by off‐target toxicity caused by the whole‐body permeation distribution of these oral drugs. As an emerging drug delivery technology, systemically administered nanocarriers can enhance the aqueous solubility and stability of encapsulated drugs, prolong circulation times, and deliver them efficiently to the liver, showing great promise for increasing the safety and efficacy of small molecule drugs. Furthermore, nanocarriers also accelerate the clinical translation of new therapies, such as nucleic acids and vaccines. This review article highlights the progress of nanoparticle delivery systems in anti‐HBV therapeutics and discusses the opportunities and challenges for the future development of anti‐HBV nanotherapeutics.

Mesoporous Silica as an Alternative Vehicle to Overcome Solubility Limitations.

Toxicological studies are a part of the drug development process and the preclinical stages, for which suitable vehicles ensuring easy and safe administration are crucial. However, poor aqueous solubility of drugs complicates vehicle screening for oral administration since non-aqueous solvents are often not tolerable. In the case of the anti-infective corallopyronin A, currently undergoing preclinical investigation for filarial nematode and bacterial infections, commonly used vehicles such as polyethylene glycol 200, aqueous solutions combined with cosolvents or solubilizers, or aqueous suspension have failed due to insufficient tolerability, solubility, or the generation of a non-homogeneous suspension. To this end, the aim of the study was to establish an alternative approach which offers suitable tolerability, dissolution, and ease of handling. Thus, a corallopyronin A-mesoporous silica formulation was successfully processed and tested in a seven-day toxicology study focused on Beagle dogs, including a toxicokinetic investigation on day one. Sufficient tolerability was confirmed by the vehicle control group. The vehicle enabled high-dose levels resulting in a low-, middle-, and high-dose of 150, 450, and 750 mg/kg. Overall, it was possible to achieve high plasma concentrations and exposures, leading to a valuable outcome of the toxicology study and establishing mesoporous silica as a valuable contender for challenging drug candidates.

Effect of DMSO on Structural Properties of DMPC and DPPC Liposome Suspensions.

The study and characterization of the biophysical properties of membranes and drug-membrane interactions represent a critical step in drug development, as biological membranes act as a barrier that the drug must overcome to reach its active site. Liposomes are widely used in drug delivery to circumvent the poor aqueous solubility of most drugs, improving systemic bioavailability and pharmacokinetics. Further, they can be targeted to deliver to specific disease sites, thus decreasing drug load, and reducing side effects and poor adherence to treatment. To improve drug solubility during liposome preparation, DMSO is the most widely used solvent. This raises concern about the potential effect of DMSO on membranes and leads us to investigate, using DSC and EPR, the influence of DMSO on the behavior of lipid model membranes of DMPC and DPPC. In addition, we tested the influence of DMSO on drug-membrane interaction, using compounds with different hydrophobicity and varying DMSO content, using the same experimental techniques. Overall, it was found that with up to 10% DMSO, changes in the bilayer fluidity or the thermotropic properties of the studied liposomes were not significant, within the experimental uncertainty. For higher concentrations of DMSO, there is a stabilization of both the gel and the rippled gel phases, and increased bilayer fluidity of DMPC and DPPC liposomes leading to an increase in membrane permeability.

SOLUBILITY ENHANCEMENT OF ATAZANAVIR BY HYDROTROPIC SOLUBILIZATION TECHNIQUE

Objective: The present study aims to increase the solubility and dissolution of atazanavir sulfate (ATZ) by employing a hydrotropic solubilization technique. Methods: ATZ is a poorly soluble drug classified under the biopharmaceutical classification system (BCS)-II, which accounts for its poor oral bioavailability. Different hydrotropic agents, such as urea and sodium benzoate and their combinations at different ratios were prepared. The prepared hydrotropes were systematically investigated for compatibility between the drug and excipients using Fourier Transform Infra-Red Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC) approaches. Further, in order to understand the conversion from crystalline to amorphous nature, X-ray Diffraction (XRD) and Scanning Electron Microscopy (SEM) studies were also performed. The formulation of a mixed hydrotropic mixture comprising urea (2.5% w/v) and sodium benzoate (5% w/v) exhibited a 100.35±1.7 % drug release at 0.25 h with higher dissolution efficiency as compared with other batches of individual hydrotrope, mixed hydrotropes as well as pure drug. Results: FTIR studies revealed that there is no incompatibility between the drug and the selected hydrotropes. DSC studies also confirmed the fact that there is no interaction between the drug and the hydrotropes by the disappearance of an endothermic peak. XRD studies revealed that there was a significant reduction in the intensity of peaks, indicating the conversion of crystalline to the amorphous form. The SEM studies indicated that the drug appears crystalline in the shape of an irregular tiny prismatic needle, indicating its crystallinity. At the same time, the hydrotrope mixtures appeared in agglomerated form with a porous nature, which may be accountable for its increase in solubility. The hydrotropes prepared using urea alone exhibited an increase in solubility of 4.42 folds, and the hydrotrope prepared using sodium benzoate alone exhibited an increase in solubility of 3.178 folds; the combination hydrotropes of urea and sodium benzoate exhibited an increase in solubility of 8.78 folds in water as compared to pure drug. The drug release from the mixed hydrotropes obeys zero-order kinetics with diffusion as the main mechanism. Conclusion: The present investigation concluded that the combination of hydrotropes enhanced the solubility of the aqueous soluble drug ATZ. However, in vivo studies are essential to establish its potential effect.

An empirical predictive model for determining the aqueous solubility of BCS class IV drugs in amorphous solid dispersions

Context Determining solubility of drugs is laborious and time-consuming process that may not yield meaningful results. Amorphous solid dispersion (ASD) is a widely used solubility enhancement technique. Predictive models could streamline this process and accelerate the development of oral drugs with improved aqueous solubilities. Objective This study aimed to develop a predictive model to estimate the solubility of a compound from the ASDs in polymer matrices. Methods ASDs of model drugs (acetazolamide, chlorothiazide, furosemide, hydrochlorothiazide, sulfamethoxazole) with model polymers (PVP, PVPVA, HPMC E5, Soluplus) and a surfactant (TPGS) were prepared using hotmelt process. The prepared ASDs were characterized using DSC, FTIR, and XRD. The aqueous solubility of the model drugs was determined using shake-flask method. Multiple linear regression was used to develop a predictive model to determine aqueous solubility using the molecular descriptors of the drug and polymer as predictor variables. The model was validated using Leave-One-Out Cross-Validation. Results The ASDs’ drug components were identified as amorphous via DSC and XRD Studies. There were no significant chemical interactions between the model drugs and the polymers based on FTIR studies. The ASDs showed a significant (p < 0.05) improvement in solubility, ranging from a 3-fold to 118-fold, compared with the pure drug. The developed empirical model predicted the solubility of the model drugs from the ASDs containing model polymer matrices with an accuracy greater than 80%. Conclusion The developed empirical model demonstrated robustness and predicted the aqueous solubility of model drugs from the ASDs of model polymer matrices with an accuracy greater than 80%.

Screening of Organic Small Molecule Excipients on Ternary Solid Dispersions Based on Miscibility and Hydrogen Bonding Analysis: Experiments and Molecular Simulation.

The preparation of solid dispersions by mixing insoluble drugs with polymers is the main way to improve the aqueous solubility of drugs. The introduction of organic small molecule excipients into binary solid dispersions is expected to further enhance drug solubility by regulating intermolecular hydrogen bonding within the system at the microscopic level. In this study, we used carbamazepine (CBZ) as the target drug and polyvinylpyrrolidone as the solid dispersion matrix and screened the third component from 13 organic small molecules with good miscibility in the solid dispersion based on the principle of similarity of solubility parameters. The hydrogen bonding parameters and dissociation Gibbs free energy of the 13 organic small molecule-CBZ dimer were calculated by quantum mechanical simulation, and the tryptophan (Try) was identified as the optimal third component of organic small molecule. The migration of CBZ in binary and ternary systems was also analyzed by molecular dynamics simulation. On this theoretical basis, the corresponding solid dispersions were prepared, characterized, and tested for solubility analysis, which verified that the drug solubility was stronger for the system with the addition of polar fractions and the Try was indeed the best third component of organic small molecule compound, which was consistent with the simulation predictions. This screening method may provide theoretical guidance for drug modification design and clinical studies.

Employing artificial neural networks for the assessment of the aqueous solubility of drug –like substances

This research has advanced Quantitative Structure-Property Relationship (QSPR) models for predicting the aqueous solubility of drug-like substances. By integrating multivariate regression and neural network techniques, the study utilized the backward algorithm to strategically select 2D and 3D molecular descriptors, resulting in the development of an optimal QSPRMLR model with k = 23. The artificial neural network regression model(QSPRANN), derived from selected descriptors of the multivariable linear regression model(QSPRMLR), demonstrated enhanced predictive capabilities for logS values in both validationand prediction groups, yielding SE values of 0.786 and 0.808, respectively. The QSPRANNsignificantly improved the overall predictability of the multivariate regression model. Statistical assessments of the QSPRANN model revealed SE = 0.699, R2train = 0.918, and Q2v = 0.878. The predicted logS values from the QSPRANN model align well with experimental data,confirming the reliability and accuracy of the developed model.

Pre-formulation of an additive combination of two antimicrobial agents, clofazimine and nisin A, to boost antimicrobial activity.

According to the World Health Organization, antimicrobial resistance is one of the top ten issues that pose a major threat to humanity. The lack of investment by the pharmaceutical industry has meant fewer novel antimicrobial agents are in development, exacerbating the problem. Emerging drug design strategies are exploring the repurposing of existing drugs and the utilization of novel drug candidates, like antimicrobial peptides, to combat drug resistance. This proactive approach is crucial in fighting global health threats. In this study, an additive combination of a repurposed anti-leprosy drug, clofazimine, and an antimicrobial peptide, nisin A, are preformulated using liquid antisolvent precipitation to generate a stable amorphous, ionized nanoparticle system to boost antimicrobial activity. The nanotechnology aims to improve the physicochemical properties of the inherently poorly water-soluble clofazimine molecules while also harnessing the previously unreported additive effect of clofazimine and nisin A. The approach transformed clofazimine into a more water-soluble salt, yielding amorphous nanoparticles stabilized by the antimicrobial peptide; and combined the two drugs into a more soluble and more active formulation. Blending pre-formulation strategies like amorphization, salt formation, and nanosizing to improve the inherent low aqueous solubility of drugs can open many new possibilities for the design of new antimicrobial agents. This fusion of pre-formulation technologies in combination with the multi-hurdle approach of selecting drugs with different effects on microbes could be key in the design platform of new antibiotics in the fight against antimicrobial resistance.

A COMPREHENSIVE REVIEW OF THE SELF-EMULSIFYING DRUG DELIVERY SYSTEM (SEDDS) AND ITS RECENTLY DEVELOPED FORMULATIONS

Background: Poor water solubility of the therapeutic compounds has become a very challenging issue for the delivery of drugs through conventional approaches. Over 40% of newly discovered active compounds also have a lack of water solubility and are lipophilic in nature. One approach for increasing the oral bioavailability of therapeutic agents is to deliver the drug via a self-emulsifying drug delivery system (SEDDS). Although many studies have been carried out, there are few drug products on the pharmaceutical market formulated as SEDDS, confirming the difficulty of formulating hydrophobic drug compounds into such formulations. Objectives: This review aims to describe the SEDDS formulation, its composition, as well as the manufacturing techniques and recently developed formulations, and also highlights an important characterization test for the evaluation of SEDDS. Methodology: Relevant literature was searched in English using different databases, i.e. Google Scholar, PubMed, and Scopus. Results: Within recent years, SEDDS was also discovered for oral administration of hydrophilic macromolecular drugs such as peptides, proteins, polysaccharides and pDNA. SEDDS are stable blends of surfactants, oils, solvents, and co-solvents. This system of drug delivery is useful for improving the aqueous solubility of drugs. They could be manufactured by the spray cooling method, the melt granulation process, the lyophilization technique, and by extrusion or spheronization. Various characterization tests, such as zeta potential, viscosity, dispersibility, cloud test, percentage transmittance, etc., could also be performed to confirm the stability of the SEEDS. Conclusion: Recently, many formulations have been developed for the delivery of drugs through the use of SEEDS and have shown increased bioavailability of the drug, as well as many promising outcomes.

Comparison of the liquisolid technique and co-milling for loading of a poorly soluble drug in inorganic porous excipients

Drug loading into mesoporous carriers may help to improve the dissolution of poorly aqueous-soluble drugs. However, both preparation method and carrier properties influence loading efficiency and drug release. Accordingly, this study aimed to compare two preparation methods: formulation into liquisolid systems (LSS) and co-milling for their efficiency in loading the poorly soluble model drug cyclosporine A (CyA) into mesoporous magnesium aluminometasilicate Neusilin® US2 (NEU) or functionalized calcium carbonate (FCC). Scanning electron microscopy was used to visualize the morphology of the samples and evaluate the changes that occurred during the drug loading process. The solid-state characteristics and physical stability of the formulations, prepared at different drug concentrations, were determined using X-ray powder diffraction. In vitro release of the drug was evaluated in biorelevant media simulating intestinal fluid. The obtained results revealed improved drug release profiles of the formulations when compared to the milled (amorphous) CyA alone. The dissolution of CyA from LSS was faster in comparison to the co-milled formulations. Higher drug release was achieved from NEU than FCC formulations presumably due to the higher pore volume and larger surface area of NEU.