Drug-excipient Interactions Research Articles

Balancing competing objectives in bigel formulations using many-objective optimization algorithms and different decision-making methods

Many-objective optimization, which deals with balancing multiple competing objectives to find compromised solutions, is essential for solving complex problems. This study explores evolutionary algorithms for optimizing the microstructural, rheological, stability, and drug release properties of bigel systems formulated using structured almond oil, mixed organogelators, and carbopol. The oleogel was identified as the dispersed phase, with droplet sizes ranging from 1.43 µm to 7.37 µm, indicating improved characteristics compared to other bigels. Each formulation exhibited non-Newtonian shear-thinning and thixotropic behaviors, which were positively influenced by the proportions of the excipients. After undergoing multiple stress cycles, highly concentrated bigels exhibited phase separation. Unexpectedly, bigels with lower viscosity exhibited reduced rates of drug release. FT-IR and HPLC analyses confirmed the compatibility and stability of drug-excipient interactions, with impurities remaining below 4%. This study emphasizes the complex interactions within mixed lipid-based bigels, requiring many-objective optimization techniques to address conflicting objectives. The objectives of optimization involve simultaneously minimizing microstructural properties while maximizing structural recovery and drug release properties. This led to conflicting objectives, where achieving higher structural recovery did not align with the desired drug release rate. Additionally, more stable formulations did not meet the optimal microstructural objectives. To resolve these conflicts, an RSM-MaOEAs approach was applied, employing various decision-making methods. Among EAs, RSM-RVEA notably achieved exceptional convergence. Furthermore, three MaOEAs-integrated decision-making methods—WSM, WPM, NED—and the RSM-desirability, offered potential solutions. Overall, this research proposes a robust framework for compromising the bigels’ performance and stability, with broader applications in drug delivery and related fields.

Development and In Vitro Evaluation of Nanoparticles of Silymarin Using Central Composite Design

Silymarin is a phytoconstituent derived from the plant Silybum marianum with poor oral absorption and bioavailability but possesses hepatoprotective activity, anticancer activity, cardioprotective, neuroprotective, stabilizing, anti-inflammatory, and antioxidant activity. Therefore, the current work aims to develop a nanoformulation of silymarin to increase bioavailability, reduce dosing frequency, minimize toxicity, and improve patient compliance. Silymarin nanoparticles were created via the ionic gelation technique, employing chitosan and TPP as the primary polymers. A central composite design was employed for formulation optimization. Chitosan and TPP were employed as independent variables, while particle size and encapsulation efficiency were considered as dependent variables. The prepared nanoparticles were evaluated through entrapment efficiency, in vitro drug release, and drug-excipient interaction studies. Thirteen experiments were conducted using the experimental runs created by the central composite design. The average particle size was between 149nm and 294nm. The encapsulation efficiency percentage was between 65.4% and 87.3%. The polydispersity index had a value of 0.437. The zeta potential of the optimized formulation was determined to be 38.1 mV. The compatibility studies between the drug and excipients were confirmed using Fourier Transform Infrared Spectroscopy and Differential Scanning Calorimetry. The successful encapsulation of silymarin within the polymer core was verified through scanning electron microscopy analysis. The silymarin-loaded nanoparticles were observed to have a significant drug release of 98,942.43% over 24 hours. The outcomes of the study of Silymarin nanoparticles showed a substantial increase in the dissolution rate, which can be ascribed to the changed solubility properties of the drug. This result is consistent with the stated aim of improving drug absorption. Keywords: Silymarin, nanoformulation, central composite design.

Solubility and Bioavailability Enhancement of a Novel Liquisolid Compact of Gliclazide

The study investigates the use of liquisolid compacts, a revolutionary pharmaceutical formulation technique, to improve the dissolution rate of weakly water-soluble medicines, with gliclazide as a case study. Nonvolatile solvents such as polyethylene glycol (PEG) 400, tween 80, and propylene glycol were used to make liquidsolid tablets, together with carrier ingredients such as Avicel PH102, starch, or HPMC, and Aerosil 200 as a coating material. The drug-excipient interaction was studied utilizing techniques such as differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). The produced tablets were tested for appearance, weight fluctuation, hardness, friability, drug content, and in-vitro drug release before being compared to traditional tablets (control) to determine the improvement in dissolution rate. The optimum formulation was subjected to stability tests. FTIR and DSC investigations revealed no significant drug-excipient interactions. All pill formulations met the requirements. Liquisolid tablets significantly increased gliclazide dissolving when compared to conventional tablets, which was ascribed to improved wetting qualities and particle effective surface area. According to the study, the liquisolid technique is a potential approach for increasing the dissolving rate of poorly soluble pharmaceuticals. The tablets remained stable at accelerated settings for three months, demonstrating the efficacy and feasibility of the liquisolid approach in increasing gliclazide dissolving rates.

Methods Development and Validation for the Estimation of Pioglitazone HCl in Bulk and Formulations by UV Spectroscopy and FTIR

The use of spectroscopic analysis, particularly UV spectrophotometer, is a simple and essential technique for bulk drug estimation, formulation studies, and compatibility assessments of drugs with various excipients. In the pharmaceutical industry, various analytical instruments, including Fourier transform infrared spectroscopy (FTIR), are employed for investigating drug-excipient interactions that can impact the stability of active pharmaceutical ingredients. This study aimed to develop a UV spectrophotometric method for the analysis of Pioglitazone hydrochloride in phosphate buffer (pH 7.4) and methanolic solution, assessing its linearity and compliance with Beer's Law. Furthermore, we aimed to use FTIR to characterize potential interactions between Pioglitazone and common pharmaceutical excipients, such as Guar Gum, Chitosan, and Sodium Alginate. Standard solutions of Pioglitazone were prepared in phosphate buffer (pH 7.4) and methanol. UV spectrophotometer was conducted to determine the maximum absorption wavelength. Calibration curves were constructed to evaluate linearity and adherence to Beer's Law. FTIR analyses were performed to investigate drug-excipient interactions by examining the functional groups. In phosphate buffer (pH 7.4), the maximum absorption wavelength for Pioglitazone hydrochloride was 268 nm. The calibration curve for Pioglitazone in phosphate buffer (pH 7.4) demonstrated linearity in the concentration range of 1–20 µg/ml, with a correlation coefficient of 0.998. In methanol, the maximum absorption wavelength for Pioglitazone hydrochloride was found to be 272 nm. The calibration curve in methanol exhibited linearity in the range of 1–20 µg/ml, with a correlation coefficient of 0.999. FTIR analysis revealed potential drug-excipient interactions, particularly in the case of Guar Gum, Chitosan, and Sodium Alginate, suggesting the formation of stable hydrogen bonds. The developed UV spectrophotometric method for Pioglitazone analysis is a reliable, cost-effective, and reproducible approach, making it a valuable tool for drug development and quality control. Additionally, the FTIR characterization confirmed interactions between Pioglitazone and common pharmaceutical excipients, enhancing our understanding of formulation compatibility.

Clove volatile oil-loaded nanoemulsion reduces the anxious-like behavior in adult zebrafish.

Clove volatile oil (CVO) and its major compound, eugenol (EUG), have anxiolytic effects, but their clinical use has been impaired due to their low bioavailability. Thus, their encapsulation in nanosystems can be an alternative to overcome these limitations. This work aims to prepare, characterize and study the anxiolytic potential of CVO loaded-nanoemulsions (CVO-NE) against anxious-like behavior in adult zebrafish (Danio rerio). The CVO-NE was prepared using Agaricus blazei Murill polysaccharides as stabilizing agent. The drug-excipient interactions were performed, as well as colloidal characterization of CVO-NE and empty nanoemulsion (B-NE). The acute toxicity and potential anxiolytic activity of CVO, EUG, CVO-NE and B-NE against adult zebrafish models were determined. CVO, EUG, CVO-NE and B-NE presented low acute toxicity, reduced the locomotor activity and anxious-like behavior of the zebrafish at 4 - 20mgkg-1. CVO-NE reduced the anxious-like behavior of adult zebrafish without affecting their locomotor activity. In addition, it was demonstrated that anxiolytic activity of CVO, EUG and CVO-NE is linked to the involvement of GABAergic pathway. Therefore, this study demonstrates the anxiolytic effect of CVO, in addition to providing a new nanoformulation for its administration.

Formulation and Evaluation of Ornidazole Oral Re-Constitutable Suspension

Large numbers of drugs are available in the market in form of dry syrup, where reconstitution has to be done by patient. Ornidazole is an antibiotic used to treat some protozoan infections. It has also been investigated for use in Crohn's disease after bowel resection. In the present investigation the drug Ornidazole was selected for the design of oral reconstitutable suspension for improving its stability and palatability by using various techniques like physical mixing, solvent evaporation and co-grinding method with different suspending agents like Xanthan gum, SCMC, Guar gum and sodium alginate. The reconstitutable suspensions were evaluated for flow properties, particle size, pH, viscosity, sedimentation volume, redispersibility and drug release by in-vitro dissolution studies. Formulated OFS reconstitutable suspension has acceptable sedimentation properties. The drug excipients interactions and crystal morphology of optimized reconstitutable suspension were evaluated by Fourier transform infrared spectroscopy (FTIR), differential scanning Calorimetry (DSC), analysis. The results indicated that the release of the Ornidazole was rapid from all formulations than the pure drug. The drug release from the suspensions followed first order kinetics. From the results it is concluded that effective taste masking of Ornidazole was achieved using SCMC and successfully evaluated in reconstitutable suspension.

Characterization of Degradation Products and Drug–Excipient Interaction Products of Erdafitinib by LC–Q-TOF-MS/MS and NMR

Characterization of Degradation Products and Drug–Excipient Interaction Products of Erdafitinib by LC–Q-TOF-MS/MS and NMR

DEVELOPMENT AND CHARACTERIZATION OF SELF-HEALING TRANSDERMAL PATCH OF LIDOCAINE FOR THE MANAGEMENT OF PAIN

Pain management is a significant challenge due to the side effects associated with commonly prescribed medications like NSAIDs and opioids. Local anesthetics, such as lidocaine, offer an alternative with fewer side effects when formulated in topical patches. Transdermal delivery systems, including heated patches, enhance drug absorption and provide targeted pain relief. This research paper aims to develop and characterize a self-heating transdermal patch of lidocaine for pain management. The drug sample of lidocaine was characterized using UV-visible spectrophotometric analysis, melting point determination, and differential scanning calorimetry. The results confirmed the purity of the drug sample. Pre-formulation studies were conducted to determine the solubility and partition coefficient of lidocaine, as well as drug-excipient interaction studies. The formulation of the lidocaine transdermal patch included the selection of excipients such as solvents, adhesives, solubilizers, and permeation enhancers. The patch was developed in three trial batches, with the final batch prepared using a drug-in-adhesive type approach. The developed patch was evaluated for physical characteristics, solvent residual content, rolling ball test, shear strength, drug crystallization, drug content, and in-vitro permeation. The results of the evaluation showed that the developed lidocaine transdermal patch had the desired physical characteristics, uniform thickness, good folding endurance, and appropriate solvent residual content. It exhibited satisfactory rolling ball test and shear strength. Microscopic examination confirmed the absence of drug crystallization. The drug content of the patch was determined to be within the desired range, and the in-vitro permeation study demonstrated successful drug release through the dialysis membrane. In conclusion, the development and characterization of a self-heating transdermal patch of lidocaine for pain management provide a promising approach for effective and targeted pain relief. The patch formulation demonstrated suitable physical properties, drug content, and permeation characteristics, suggesting its potential as an alternative pain management solution. KEYWORDS: Lidocaine, transdermal patch, pain management, self-heating, drug delivery

Transferosomal gel for transdermal delivery of insulin: Formulation development and ex vivo permeation study

The study was to develop a transdermal formulation of insulin, determine its pharmaceutical characteristics, and finally test its efficacy. In the current study - Transfersomes were selected as the carrier system for insulin. The transfersomes were produced by the hand-shaking method using soy lecithin phospholipid and sodium deoxycholate as the objective of the surfactant. The prepared transfersomes were subjected to characterization with optical microscopy and scanning electron microscope to estimate the shape and size of transfersomes respectively. In addition, the physical and drug-excipient interaction studies were carried out and the transfersomes were also studied for the insulin entrapment efficiency.Results of the study showed the shape of the transfersomes was well defined and spherical. The mean size of transfersomes was estimated to be 130 ​nm The transfersomes were found to be stable over a period of four weeks. The insulin entrapment efficiency of the transfersomes was estimated to be 87.3%. The ex-vivo skin permeation study employing goat ear skin with the transfersomes hydrogel revealed that there was a slow and sustained release of insulin till 180 ​min. From the above study, it may be concluded that transfersomes are suitable carriers of insulin across biological membranes.

Fabrication and Evaluation of Amoxicillin and Potassium Clavulanate Medicated Chocolate

The purpose of this investigation was to develop a formulation of amoxicillin and potassium clavulanate in chocolate form. Amoxicillin is an antibiotic belonging to the beta-lactam family. By binding to penicillin-binding proteins, beta-lactams stimulate autolytic enzymes in the bacterial cell wall, which in turn inhibits transpeptidation (the cross-linking stage in cell wall production). The streptomyces-derived, semi-synthetic beta-lactamase inhibitor potassium clavulanate. Multiple bacterial infections may be treated well with the antibiotic combination of amoxicillin and potassium clavulanate acid. It prevents germs from multiplying. Chocolate refers to a family of sweets made by combining cocoa (cacao), cocoa butter, and sugar in various proportions to form a solid. For improved patient compliance, the medicated chocolate formulation is often utilized for pediatric administration. The traditional chocolate formulation, which includes cocoa powder, moisture content, and blooming tests, is inferior to the one that incorporates carob powder, which lowers gastrointestinal troubles. The whole medication from the F4 formulation is released within 60 minutes, leading to a wide range of GIT disorders such heartburn and acid reflux. The formulation is stable throughout chocolate formulation manufacturing, with no drug excipient interactions and no drug degradation detected. The dimensions of the finished product are 28.5mm in length, 18mm in width, and 14mm in height. Batch F4 is the finest of all batches.

Formulation and Development of Medicated Chewing Gum Containing Ondansetron and Domperidone

This study aimed to determine the feasibility of combining ondansetron and domperidone into a single medicated gum. Molded Chewing Gum (MCG) was developed via direct compression. Our medicated chewing gum was designed with diabetics in mind, and Stevia was selected for the research because it does not increase blood glucose levels. Direct compression was used in the development of medicated gum. Each formulation's permissible flow characteristics and pre-compression parameters, including bulk density, tapered density, Carr's compressibility index, and Hausner ratio, were shown. After compression, it was determined that all of the parameters were within acceptable limits, including changes in weight, thickness, appearance, and in vitro drug release. There is no indication of drug-excipient interactions based on physical testing or TLC analysis. Two plasticizers only when comparing glycerol with coconut oil, the latter proved to be the superior plasticizer. Formulation F6 was chosen as the best option since all of the attributes fall within the expected range. The results of the F6 formulation were analyzed for their thickness, weight fluctuation, appearance, and in vitro drug release. Coconut oil shown to be the superior plasticizer for making MCG after testing and evaluation. Probably because the concentration is optimized for releasing the drug from the formulation, the fact that F6 includes 24 mg of coconut oil makes it a more effective formulation.

Fabrication and Evaluation of Polymeric Nanoparticles of Acitretin for the Solubility Enhancement

The present study was an attempt to prepare nanoparticle of Acitretin which is used in Psoriasis. The preparation of nanoparticles was done by precipitation method employing several blends of polymers such as PVPK 30, PVPK 90, Poloxamer 407 and Poloxamer 188. The oral nanoparticles were characterized for various physicochemical parameters, such as particle size analysis, drug-excipient interactions, zeta potential, saturated solubility, XRD study, in-vitro drug release, FTIR spectroscopic studies displayed that there were not any interactions between drug and excipients. The nanoparticle batch F8 was found to be optimum batch based upon the outcomes obtained from the physicochemical characterization of nanoparticles. The mean particle size of nanoparticle batch F8 containing showed 96.01 % release at the end of 90 min and formulation displayed good nanoparticle strength.

Quantitative Determination of Proguanil HCl in presence of Croscarmellose Sodium by HPLC using Competitor Mechanism

A simple, precise and accurate high-performance liquid chromatographic method was developed for estimation of proguanil HCl in presence croscarmellose sodium in bulk and tablet formulation. During analysis a strong interaction between proguanil HCl and croscarmellose sodium was noticed when proguanil HCl in an aqueous solution was spiked with croscarmellose sodium. This interaction leads to retention of drug on the surface of croscarmellose sodium. To overcome the recovery issue an analytical method was set up. This method involves elimination of drug-excipient interaction by competitive inhibition followed by isocratic elution using a mobile phase consisting 0.01% o-phosphoric acid: acetonitrile (55:45v/v). Column used was Qualisil 5 BDS-C18 column (250mm x 4mm i.d., 5 µm particle size) and flow rate was 1mL/min. The detection wavelength was 257 nm. The retention time was found to be 3.821min. Linearity of the method was 10-70µg/mL. The validated method showed excellent results in terms of accuracy, precision and system suitability.

Effect of Cholesterol and Different Solvents on Particle Size, Zeta Potential and Drug Release of Eucalyptus Oil Phytosome

Pharmacognosy Research,2023,15,3,578-590.DOI:10.5530/pres.15.3.061Published:June 2023Type:Original Article Authors:Sharad Visht, and Sana Sirwan Salih Author(s) affiliations:Sharad Visht*, Sana Sirwan Salih Department of Pharmaceutics, Faculty of Pharmacy, Tishk International University, Erbil, KRG, IRAQ. Abstract:Background: Herbal extracts show poor absorption and bioavailability but their complex with phospholipids i.e., phytosome improves this major problem. Aim: The aim of research was to examine the effect of cholesterol and different organic solvents on particle size and zeta potential of eucalyptus oil phytosome. Materials and Methods: Totally six batches of phytosomes were prepared using three solvents chloroform, dichloromethane, acetone, with and without addition of cholesterol. Phytosome were evaluated for yield, FTIR, partial size and zeta potential, drug entrapment and drug release, drug release kinetics and stability studies. Results: The yield, density refractive index and maximum absorbance (λmax) of eucalyptus oil was found to be 1.65±0.74%, 0.9928 g/cm³ (24.2°C), 1.3613(24.6°C), and 297.733 nm respectively. There was no drug excipient interaction. The yield varied from 85.14±0.74 to 87.14±0.74%, particle size varied from 71.76±0.63 to 197.36±0.53 nm, zeta potential varied from 15.3±0.27 to-28.2±0.26 mV and entrapment efficiency varied from 57.45±0.35 to 67.34±0.52 respectively. The in vitro drug release varied from 87.26±0.63 to 71.35±0.63% up to 300 min (5 hr) and batch-A was selected as best formulation that showed Peppas Korsmeyer as the best fit model with R2 value 0.9422 and mechanism of drug release was Fickian Diffusion (Higuchi Matrix). The stability studies showed 99.14±0.25 to 99.55±0.52% drug content on 28th day. Conclusion: The particle size of phytosomes was increased on addition of cholesterol. The acetone showed the smallest particle size and chloroform showed the biggest particle size that indicated that molecule diameter and molecular weight affects the solubility and assembly of phospholipid/ cholesterol in solvent in order to prepare particulate drug delivery system Keywords:Eucalyptus, Evaluation, Particle size, Phytosomes, Zeta potential.View:PDF (1 MB)

Critical Strategies for Drug Precipitation Inhibition: A Review with the Focus on Poorly Soluble Drugs.

An oral route for drug administration is a more suitable route because of its ease of administration, pain avoidance, patient compliance, accommodation of various types of drug molecules, etc. But there are many factors affecting the oral absorption of the drugs. The main factor associated with oral absorption is drug solubility. Many new chemical molecules are poorly soluble in nature and can be included in BCS classes II and IV. For the administration of these drugs through the oral route, it was found that solubility is the rate limiting step. The low solubility of these drugs tends to cause precipitation in the gastrointestinaltract (GIT), affecting their bioavailability. Drug precipitation may be triggered by many factors such as insolubility of the drug in co-solvent, drug-excipient interactions, physiochemical properties of the drug, sudden change in the pH of the environment, incompatibility with the surfactant, etc. Precipitation of a drug may occur in two stages, formation of nucleation and crystal growth. To overcome precipitation, there are many strategies such as the use of polymers, the addition of surfactants, modulating drug loading and solubilizing capacity, change in the pH of the environment, etc. In this review, the causes of precipitation and diverse strategies of precipitation inhibition are critically reviewed.

Topic - Controlled Drug Release by Excipient Modification: A Review

Excipients play an essential role in the physical and chemical characteristics of the oral dosage form. The excipient modification can alter the parameters like dissolution and disintegration. Oral dosage form passes through the varying pH of the human gastrointestinal tract and delivers the drug at a specific site. For providing pH-responsive dosage form, novel techniques are used, which include hydrogels, nanoparticles, and microspheres. The article also reviews problems related to drug excipient interactions and questions related to delivering the drug to specific targets by showing pH-responsive drug release. The addition of excipients like lignin can achieve a better pH modified version and controlled release of the active pharmaceutical excipient. The biopolymer lignin can be altered due to many functional groups in its chemical structure. The use of lignin can help to release the drug in specific targets within the gastrointestinal tract. The use of natural polymers should be increased to manufacture eco-friendly and economical dosage forms.

Manipulating drug release from 3D printed dual-drug loaded polypills using challenging polymer compositions

Combining multiple medications in a single dosage form has emerged as an important strategy for treating complex diseases and could help tackle the growing issue of polypharmacy. In this study we investigated the suitability of different dual-drug designs for achieving simultaneous, delayed and pulsatile drug release regimes using two model formulations: an immediate release erodible system of Eudragit E PO loaded with paracetamol; and an erodible swellable system of Soluplus loaded with felodipine. Both binary formulations, despite not fused deposition modelling (FDM) printable, were successfully printed using a thermal droplet-based 3D printing method, Arburg Plastic Freeforming (APF), and exhibited good reproducibility. X-ray powder diffraction (XRPD), Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) and Differential Scanning Calorimetry (DSC) were used to assess drug-excipient interaction. The printed tablets were evaluated for drug release using in vitro dissolution testing. We found the simultaneous and delayed release designs were effective at generating the intended drug release profiles, giving insight into the types of dual-drug designs which can be used to create complex release profiles. In contrast the pulsatile tablet release was non-defined, highlighting the design limitations when using erodible materials.

Merging konjac glucomannan with other copolymeric hydrogels as a cutting-edge liquid raft system for dual delivery of etoricoxib and famotidine

This study aimed to formulate and evaluate a floating raft system for the co-delivery of etoricoxib (ETO) and famotidine (FAM) using a combination of glucomannan with natural/semi-synthetic polysaccharides. Formulation variables affect gelation lag time (GLT), floating lag time (FLT), and release percentage of drugs after 1–8 h, Stability, and viscosity parameters were evaluated. In vivo X-ray studies, followed by the pharmacokinetic study, were performed on human volunteers. Formulations exhibited pseudoplastic behavior for ease of swallowing. The optimum raft system (ORS) comprised 1% Na alginate, 0.1% Low Methoxyl (LM) pectin, 0.8% Konjac glucomannan (KGL), 1% Precirol, and 1% CaCO3. ORS exhibited rapid GLT and FLT (around 42 and 8 sec respectively) in 0.1 N HCl as well as controlled release of ETO (15% in 1 h and 82% in 8 h) and FAM (29% in 1 h and 85% in 8 h). Formulation stability with the absence of any drug-excipient interactions was observed. The X-ray imaging showed a promising buoyancy ability for approximately 8 h. Compared with marketed products, ORS showed superior relative bioavailability for both drugs. These findings revealed the successful preparation of a promising raft system with improved dual drug delivery.

DE-INTERACT: A machine-learning-based predictive tool for the drug-excipient interaction study during product development—Validation through paracetamol and vanillin as a case study

The compatibility of drugs with excipients plays a crucial role in the prospective stability of pharmaceutical formulations. Apart from real-time stability studies, conventional analytical tools like DSC, FTIR, NMR, and chromatography help identify the possibilities of drug-excipient interactions. Machine learning can assist in developing a predictive tool for drug-excipient incompatibility. In the present work, PubChem Fingerprint is employed as the descriptor of compounds that thoroughly represents the drug's and excipient's chemistry. The 881-bit binary fingerprints of each drug and excipient make 1762 inputs, and one categorical output makes an instance in the dataset. A dataset of more than 3500 instances of drugs and excipients is carefully selected from peer-reviewed research papers. Rigorous training of the Artificial Neural Network (ANN) model was performed with maximum validation accuracy, minimum validation loss, and maximum validation precision as the checkpoints. The machine learning model (DE-Interact) was trained, achieving training and validation accuracies of 0.9930 and 0.9161, respectively. The performance of the DE-Interact model was evaluated by confirming three incompatible predictions by conventional analytical tools. Paracetamol with vanillin, paracetamol with methylparaben, and brinzolamide with polyethyleneglycol are these instances which are predicted as incompatible by the DE-Interact. DSC, FTIR, HPTLC, and HPLC analysis confirm the prediction. The present work offers a reliable DE-Interact tool for quick referencing while selecting excipients in formulation design.

Assessment of Solid-State Behaviour and in vitro Release of Artemether from Liquisolid Compact Using Mesoporous Material as an Excipient

Abstract: Background: Artemether is a potent antimalarial drug used in the first-line treatment of multi-drug-resistant malaria. It belongs to BCS II, exist in different polymorphic forms, and exhibits incomplete absorption and low oral bioavailability owing to poor dissolution. Aim: The present study evaluates the effect of different mesoporous materials in the liquisolid compact for the augmentation of dissolution of the drug, and polymorphic stability. Materials and Methods: In the liquisolid compact Tween 80 was used as a non-volatile solvent for the dispersion of the drug, microcrystalline cellulose as carrier, and Syloid244FP and SyloidXDP as coating materials at different coating and carrier ratios. Eight such formulations were prepared. The formulated liquisolid compact was evaluated for precompression parameters, followed by direct compression process. The tablets thus prepared were assessed for hardness, friability, wetting time, in-vitro dissolution, and stability studies. Physico-chemical characterization was done to study drug excipient interaction, thermal behaviour, and surface characteristics. Results and Discussion: The study revealed that an increasing quantity of mesoporous material exhibited a better release profile compared to the pure drug. Good compressibility and tablet ability were observed at a carrier and coating materials ratio of 1:5. Compatibility between the drug and excipients was established from the FTIR study. Noteworthy findings of PXRD and DSC suggested the presence of artemether in metastable β form in the formulations. Short-term stability of the formulations was established. Conclusion: Hence, the approach of liquisolid compact using mesoporous silicas at a suitable excipient ratio could be an optimistic approach for the enhancement of dissolution and stability of artemether. Keywords: Artemether, Liquisolid compact, Solid-state behaviour, Dissolution, Mesoporous silica.