Drug-receptor Interactions Research Articles

Characterization of Drug Delivery Systems by Transmission Electron Microscopy.

The contribution of electron microscopy, and here, in particular transmission electron microscopy (TEM), to the formulation and understanding of the biological action of drug delivery systems has led to a better insight into the design principles of drug delivery systems. TEM can be applied for particle characterization, for the visualization of the uptake and intracellular pathways of drug vehicles in cells and tissues and more recently can be also applied for the high-resolution investigation of drug-receptor interactions with near-atomic resolution. This chapter introduces basic techniques to optimize imaging quality of soft matter samples, highlights possibilities to study certain aspects of drug delivery applications, and finally provides a short introduction to high-resolution characterization possibilities which recently emerged.

Synthesis, Characterization, Docking Studies and Antiepileptic Activity of Novel Piracetam Derivatives

Piracetam is a nootropic drug that has been used in clinical trials for decades, but is still a mystery due to a lack of understanding of its mechanism of action. In this research, sixteen novel piracetam derivatives were synthesized in three steps and characterized by IR, NMR and mass spectroscopic techniques. Based on the docking studies, two derivatives were identified as more active based on the drug receptor interactions studies and were further subjected to animal studies for the evaluation of the activity. Compounds 6 and 10 had shown a strong anticonvulsant activity based on the molecular docking studies. It was hypothesized from the synthesized analogues that the non-substitution with thio moiety at has a major effect on reducing the contagiousness of seizure discharge and increasing the seizure threshold.

Synthesis, crystallographic, quantum chemical and molecular docking studies of 4-benzoyl-1,2,3,11a-tetrahydro-6H-chromeno[3,2-e]imidazo[1,2-a]pyridin-6-one

The synthesis of pyridine derivatives is an active area of research in the development of new drugs. In view of the above importance, a novel compound with fused rings of derivatives of biologically active imidazole, pyridine and chromanone was synthesized. The crystal structure was analysed by single crystal X-ray diffraction method. The quantum chemical parameters of the molecule in the gaseous state were calculated by semi-empirical method using restricted Hartree-Fock wavefunction. The physicochemical properties such as druglikeness and bioactive scores were predicted to understand the drug transport and receptor interactions. Molecular docking studies were performed to analyze the binding of this compound with various bacterial and fungal pathogens. This study points out the potential of this compound to act as an antimicrobial agent. Comparison with related compounds shows that the addition of more number of biologically active groups enhances the activity.

Endophytic bacteria of Fagonia indica Burm. f revealed to harbour rich secondary antibacterial metabolites.

Endophytic bacteria are the source of novel bioactive compounds, used as therapeutic agent. Molecular docking is a computational technique use frequently, to find novel drugs targets and drugs-receptors interactions. The current study was designed to isolate and identify endophytic bacteria for the extraction of bioactive compounds. Further, to characterized extracts and to explore compounds interactions with bacterial cell wall and outer membrane synthesizing proteins. Endophytes were identified using 16s rRNA amplification technique. For bioactive compounds, solvent extraction method was followed and characterized further through GC-MS analysis. To find targets and drugs-receptors interactions, molecular docking studies and biological assays were performed. The isolated endophytes belong to five different genera namely Enterobacter, Bacillus, Erwinia, Stenotrophomonas and Pantoea. In case of antibacterial assay Stenotrophomonas maltophilia extract showed significant inhibitory zones (15.11±0.11mm and 11.3±0.16) against Staphylococcus caseolyticus and Acinetobacter baumanni, with MIC 33.3 and 50μg/mL respectively. Among the characterized fifty compounds, from endophytic bacteria "antibacterial compound" N-(5-benzyl-10b-hydroxy-2-methyl-3,6-dioxooctahydro-8H-oxazolo[3,2-α] pyrrolo[2,1c] pyrazin-2-yl)-7-methyl2,3,3a,3a1,6,6a,7,8,9,10,10a,10b-dodecahydro-1H-4λ2-indolo[4,3-fg]quinoline-9-carboxamide of bacteria Stenotrophomonas maltophilia were an excellent binder with MurF ligase active site, with binding energy of -10.2 kcal/mol. Extracts of endophytic bacteria composed of various pharmacologically active ingredients such as antibacterial compounds. Molecular docking studies provide important information regarding drug-receptor interaction, thus can be used in novel drug discovery.

Evaluation of Candidatus Liberibacter Asiaticus Efflux Pump Inhibition by Antimicrobial Peptides.

Citrus greening, also known as Huanglongbing (HLB), is caused by the unculturable bacterium Candidatus Liberibacter spp. (e.g., CLas), and has caused a devastating decline in citrus production in many areas of the world. As of yet, there are no definitive treatments for controlling the disease. Antimicrobial peptides (AMPs) that have the potential to block secretion-dependent effector proteins at the outer-membrane domains were screened in silico. Predictions of drug-receptor interactions were built using multiple in silico techniques, including molecular docking analysis, molecular dynamics, molecular mechanics generalized Born surface area analysis, and principal component analysis. The efflux pump TolC of the Type 1 secretion system interacted with natural bacteriocin plantaricin JLA-9, blocking the β barrel. The trajectory-based principal component analysis revealed the possible binding mechanism of the peptides. Furthermore, in vitro assays using two closely related culturable surrogates of CLas (Liberibacter crescens and Rhizobium spp.) showed that Plantaricin JLA-9 and two other screened AMPs inhibited bacterial growth and caused mortality. The findings contribute to designing effective therapies to manage plant diseases associated with Candidatus Liberibacter spp.

Exploration of Chemopreventive Potential of Linalool in Targeting Lung Cancer Biomarkers.

Phytochemicals are used to treat lung cancer in contemporary and traditional medicine. The limitations of known chemotherapeutic drugs such as non-specificity, resistance, and toxicity restrict their use for lung cancer treatment. Therefore, the search for target-specific novel entities is required continuously. Linalool, a monoterpene alcohol that possesses antiviral, anti-inflammatory, and antibacterial properties, is present in sweet basil, laurel, jasmine, rosewood, and lavender. Previous reports revealed its anticancer potential against colon, breast, and liver cancer. In this study, linalool's efficacy in targeting biomarkers associated with different lung cancer stages has been investigated. The in silico molecular docking analysis was used to explore drug-receptor interaction, and further, linalools cytotoxicity potential was evaluated on lung adenocarcinoma cell line (A549). The toxicity profiling of linalool was done by ADMET analysis. In the results, Linalool revealed an excellent binding affinity with the selected targets. It showed the highest interaction with BRAF with the binding energy of -5.6 kcal/mol. Furthermore, it successfully interacts within the binding pocket of BRAF, similar to its inhibitor (Sorafenib). In MTT analysis, linalool significantly reduces the percent viability IC30 474.94 ± 43.12, 379.33 ± 49.5, and 183.77 ± 66.7 μM in A549 cell lines for 24, 48, and 72 h, respectively. These results concluded that linalool possesses chemopreventive potential against lung cancer by interacting or modulating selected biomarkers associated with a lung cancer diagnosis, progression, and proliferation.

Biosensing Tacrolimus in Human Whole Blood by Using a Drug Receptor Fused to the Emerald Green Fluorescent Protein.

Tacrolimus (FK506) is an immunosuppressant drug (ISD) used to prevent organ rejection after transplantation that exhibits a narrow therapeutic window and is subject to wide inter- and intra-individual pharmacokinetic fluctuations requiring careful monitoring. The immunosuppressive capacity of FK506 arises from the formation of a complex with immunophilin FKBP1A. This paper describes the use of FKBP1A as an alternative to common antibodies for biosensing purposes. Bioassays use recombinant FKBP1A fused to the emerald green fluorescent protein (FKBP1A-EmGFP). Samples containing the immunosuppressant are incubated with the recombinant protein, and free FKBP1A-EmGFP is captured by magnetic beads functionalized with FK506 to generate a fluorescence signal. Recombinant receptor-drug interaction is evaluated by using a quartz crystal microbalance and nuclear magnetic resonance. The limit of detection (3 ng mL-1) and dynamic range thus obtained (5-70 ng mL-1) fulfill therapeutic requirements. The assay is selective for other ISD usually coadministered with FK506 and allows the drug to be determined in human whole blood samples from organ transplant patients with results comparing favorably with those of an external laboratory.

In Silico Design of Molecular Analogues of 2-Butyl-5- pentylbenzene-1,3-diol (Stemphol) as Drug Prototypes for Treatment of Chemical Dependents of Cannabis Sativa

Background: The chemical dependency caused by recreational drug abuse is highly detrimental to humans and has direct implications for society. Cannabis sativa is still at the top of the ranking of most used drugs in the world, and its major chemical component is Δ9-THC. This molecule is the main cause of addiction in chronic users, and its action is measured by the CB1 receptor present in the CNS. So far there is no approved drug for the treatment of abstinence in C. sativa. Objective: In this sense, the objective of this research is to propose analogues of the Stemphol (2-methyl-5-pentylbenzene-1,3-diol) molecule that can serve as treatment for withdrawal crises in C. sativa addicts, initially through in silico methods. Methods: 28 structural modifications were carried out in the molecule stemphol. These were subjected to in silico predictions of pharmacokinetics, toxicology, pharmacological activity, synthetic viability and prediction of drug-receptor interaction through molecular docking. For this, the software and web servers PreADMET, DEREK 2.1, PASS, SEA, SYLVIA 2.4 and GOLD were used. Results: 22 analogues demonstrated good pharmacokinetic results and 16 analogues gave no warning of hepatotoxicity, mutagenicity, nephropathies and carcinogenicity in mammals. Biological activity predictions were performed on the PASS server, resulting in 28 analogues exhibiting adenylate cyclase inhibition and/or MAP kinase stimulating activity; in SEA, the performance of the CB1 receptor was analyzed, resulting in 20 analogues with action on CB1 receptors in humans. The selected analogues 1, 4, 16, 17, 19, 24, 25 and 26 were submitted to synthetic accessibility prediction in the SYLVIA software because they presented better results in their pharmacokinetic, toxicological and predictive properties. Conclusion: Of these, the analogues 17 and 25 obtained a very satisfactory result in the interaction with the CB1 receptor through the molecular docking method and can be considered great proposals for future in vitro and in vivo studies, with the ability to further elucidate their actions. Keywords: Chemical dependency, Cannabis sativa, Withdrawal Syndrome.

Molecular Docking Study of Novel Nitrofuran Derivatives As Urinary Tract Anti Infectives

Modern drug design commonly uses molecular docking to understand drug-receptor interaction. For docking tests against 1YLU, an E. coli nitro-reductase, substituted furan derivatives were used in the current work. The study's primary goal is to dock the chosen nitrofuran derivatives onto the protein and compare the results to those of nitrofurantoin as a standard drug. PyRx and the discovery studio visualizer (DSV) application were used to carry out the molecular docking analysis, and E. coli nitro-reductase (1YLU) was retrieved from the protein data bank (PDB) website. All seven of the nitrofuran compounds docking scores were discovered to range between -5.9 and -8.8 Kcal/mol. Compound 2a received the highest binding score, with a score of -8.80 Kcal/mol.At the protein active site, compound 2a interacts with amino acids such as glutamic acid (GLU 165), arginine (ARG 10 & 207), serine (SER 39 & 12), glutamine (GLN 142), and lysine (LYS205).Numerous nitrofuran substituted compounds have been identified for the activity and the nitrofuran derivatives have been discovered to exhibit urinary tract anti-infective activities.

Targeting human thymidylate synthase: Ensemble-based virtual screening for drug repositioning and the role of water

A drug repositioning computational approach was carried to search inhibitors for human thymidylate synthase. An ensemble-based virtual screening of FDA-approved drugs showed the drugs Imatinib, Lumacaftor and Naldemedine to be likely candidates for repurposing. The role of water in the drug-receptor interactions was revealed by the application of an extended AutoDock scoring function that included the water forcefield. The binding affinity scores when hydrated ligands were docked were improved in the drugs considered. Further binding free energy calculations based on the Molecular Mechanics Poisson-Boltzmann Surface Area method revealed that Imatinib, Lumacaftor and Naldemedine scored −130.7 ± 28.1, −210.6 ± 29.9 and −238.0 ± 25.4 kJ/mol, respectively, showing good binding affinity for the candidates considered. Overall, the analysis of the molecular dynamics trajectory of the receptor-drug complexes revealed stable structures for Imatinib, Lumacaftor and Naldemedine, for the entire simulation time.

In-silico ADME prediction and molecular docking study of novel benzimidazole-1,3,4-oxadiazole derivatives as CYP51 inhibitors for antimicrobial activity

A class of innovative benzimidazole-1,3,4-Oxadiazole derivatives is a significant heterocyclic molecule for therapeutic development. In heterocyclic chemistry, the novel 1,3,4-Oxadiazole nucleus has a wide range of uses, including antibacterial, treatment. Molecular docking is frequently employed in contemporary drug design to comprehend drug-receptor interaction. Swiss dock, PyRx, and discovery studio visualizer (DSV) tools were used to predict in-silico ADME properties. In the current investigation, substituted benzimidazole-1,3,4-Oxadiazole derivatives were taken for docking studies against 6AYB an Naegleria fowleri CYP51-ketoconazole complex. The main objective of the study is to perform docking of the selected benzimidazole-1,3,4-oxadiazole derivatives on the protein and compare the docking score with standard ketoconazole. The molecular docking study was conducted using PyRx and the discovery studio visualizer (DSV) program, Naegleria fowleri CYP51-ketoconazole complex (6AYB) was obtained from the protein data bank (PDB) site. It was found that the docking score of all sixteen 1,3,4-Oxadiazole compounds ranged from -8.1 to -8.9 Kcal/mol. The novel benzimidazole with 1,3,4-Oxadiazole derivatives has been found to possess antibacterial properties, many substituted 1,3,4-Oxadiazole derivatives have been reported for the activity

Drug-Receptor Interaction of Peptidic HIV-1 Protease: Polar Effect-II

Klopman described the chemical reaction of metal ions and base ions in term of softness, E‡n and E‡m, respectively. By simple modification of known methods, Singh et al. made it applicable for neutral Lewis acids (transition metal salts) and bases (organic molecules) and also extended its application to biological systems for site selectivity and to explain reaction mechanism (markovnikov and anti-markovnikov rule), ligand-receptor interaction of testosterones, estrogens and tetrahydroimidazobenzodiazepinone. In this study effective atomic softness E‡n(eff) and E‡m(eff), and their change ΔE‡nm have been used for site selectivity and polar interaction between 51 peptidic HIV-1 protease inhibitors and receptor amino acids. ΔE‡nm values derived from drug-receptor interaction show that when one moiety on receptor behaves as nucleophile (O of valine amino acid) at the same time maximum electrophilic site of the drug (C-atom of the maximum E‡n(eff) value) orient itself to come close the respective site and make maximum interaction, while when another moiety on receptor behaves as electrophilic site (C of isoleucine amino acid), at the same time maximum nucleophilic site of the drug (O-atom of the maximum E‡m(eff) value) also orient itself to come close the respective site and make maximum interaction.

Thermodynamic and structural profiles of multi-target binding of vinblastine in solution.

Structural information about drug-receptor interactions is paramount in drug discovery and subsequent optimization processes. Drugs can bind to multiple potential targets as they contain common chemical entities in their structures. Understanding the details of such interactions offer possibilities for repurposing and developing potent inhibitors of disease pathways. Vinblastine (VLB) is a potent anticancer molecule showing multiple receptor interactions with different affinities and degrees of structural perturbations. We have investigated the multi-target binding profile of VLB with DNA and human serum albumin (HSA) in a dynamic physiological environment using spectroscopic, molecular dynamics simulations, and quantum mechanical calculations to evaluate the structural features, mode, ligand and receptor flexibility, and energetics of complexation. These results confirm that VLB prefers to bind in the major groove of DNA with some inclination toward Thymidine residue and the TR-5 binding site in HSA with its catharanthine half making important contacts with both the receptors. Spectroscopic investigation at multiple temperatures has also proved that VLB binding is entropy driven indicating the major groove and TR-5 binding site of interaction. Finally, the overall binding is facilitated by van der Waals contacts and a few conventional H-bonds. VLB portrays reasonable conformational diversity on binding with multiple receptors.

A computational study on acetaminophen drug complexed with Mn+, Fe2+, Co+, Ni2+, and Cu+ ions: structural analysis, electronic properties, and solvent effects.

In the present research, the cation-π interactions in acetaminophen-M complexes (M = Mn+, Fe2+, Co+, Ni2+, and Cu+) are investigated using density functional theory (DFT/ωB97XD) in the gas phase and solution. The results show that the absolute values of energy are reduced in going from the gas phase to the solution. Based on the obtained data, the complexes in water are the most stable. The natural bond orbital (NBO) and the atoms in molecules (AIM) analyses are also applied to achieve more details about the nature of interactions. These results are useful for understanding the role of the drug-receptor interactions in the complexes. According to AIM outcomes, the cation-π interactions are the closed-shell and may indicate the partially covalent nature in the complexes. A comprehensive analysis is also performed on the conceptual DFT parameters of the complexes to evaluate their electronic properties. Our findings show increasing the stability and decreasing the reactivity of the complexes in the solution phase with respect to the gas phase. These interactions are ubiquitous in biological systems, and their importance in theoretical models led us to study such important interactions. The results of this study may be useful for the design and synthesis of a variety of supramolecular complexes with the desired properties.

Drug-Receptor Interaction of Peptidic HIV-1 Protease: The Hydrophobic Effect-I

When a drug interacts with its receptor, the nonpolar substituent of drug and receptor proteins attract each other because they have opposite magnitude with respect to each other. X-rays structure studies reflected that the S2/S2’ pocket in HIV-1 protease enzyme are essentially hydrophobic. The residues that make up these pockets are Val-32, Ile-47, Ile-50, and Ile-84 in each monomeric polypeptidic unit of the protease enzyme. Δπdr and ΔSASAdr have been used to measure the extent of hydrophobic interaction between peptidic protease inhibitors and receptor proteins (binding site: valine‒isoleucine; and catalytic site: glycine‒aspartic acid‒threonine) on the HIV-1 protease enzyme. For measurement of hydrophobic interaction, the molecular modeling and geometry optimization of all the inhibitors and the receptor amino acids have been carried out with CAChe Pro software by opting semiempirical PM3 methods. Log P was calculated using the atom-typing scheme of Ghose and Crippen, while solvent accessible surface area by conductor likes screening model. πd, πr, SASASd and SASASr well describe the hydrophobicities of the substituents and play the effective role for site selectivity for interaction of the drug with the receptor. Comparative study of values of Δπdr and ΔSASAdr show the order of hydrophobic interaction with respect to amino acids: Asp > Thr > Val > Ile and Thr > Val > Asp > Ile, respectively. Further, comparative study of the values of (ΣΔπdr)binding-site, (ΣΔπdr)catalytic-site, (ΣΔSASAdr)binding-site, (ΣΔSASAdr)catalytic-site shows that peptidic HIV-1-PRIs interact with binding site rather than catalytic site as binding site have lower value of ΣΔπdr and ΣΔSASAdr. Among the binding site, Val has maximum interaction than Ile, as it has lower vale of Δπdr and ΔSASAdr.

Cell membrane coated electrochemical sensor for kinetic measurements of GLUT transport

The upregulation of glucose transporter (GLUT) is a typical pathological marker in numerous cancer types and a potential target for anti-cancer drug therapy. We developed a cell membrane-based glucose sensor for real-time monitoring of GLUT transport kinetics. By combining hydrogel layers and liposomes, a planar cell membrane was constructed over the electrode, preventing pore leakage and allowing for highly sensitive and selective measurements. Based on this continuous monitoring technique, we investigated the effect of GLUT1-specific inhibitors such as Cytorelaxation B and BAY-876. We also measured the affinity of different hexoses to GLUT1 using a normalized response time comparison based on the cell membrane sensor. Experimental results were consistent with the molecular docking simulation, indicating that the sensor can be adapted to measure the glucose transport kinetics in different pharmacological conditions. This work demonstrated that cell membrane transport channels could maintain their transmembrane function in-vitro, and it has potential application in evaluating drug-receptor interaction.

Quorum sensing-based interactions among drugs, microbes, and diseases.

Many diseases and health conditions are closely related to various microbes, which participate in complex interactions with diverse drugs; nonetheless, the detailed targets of such drugs remain to be elucidated. Many existing studies have reported causal associations among drugs, gut microbes, or diseases, calling for a workflow to reveal their intricate interactions. In this study, we developed a systematic workflow comprising three modules to construct a Quorum Sensing-based Drug-Microbe-Disease (QS-DMD) database ( http://www.qsdmd.lbci.net/ ), which includes diverse interactions for more than 8,000 drugs, 163 microbes, and 42 common diseases. Potential interactions between microbes and more than 8,000 drugs have been systematically studied by targeting microbial QS receptors combined with a docking-based virtual screening technique and in vitro experimental validations. Furthermore, we have constructed a QS-based drug-receptor interaction network, proposed a systematic framework including various drug-receptor-microbe-disease connections, and mapped a paradigmatic circular interaction network based on the QS-DMD, which can provide the underlying QS-based mechanisms for the reported causal associations. The QS-DMD will promote an understanding of personalized medicine and the development of potential therapies for diverse diseases. This work contributes to a paradigm for the construction of a molecule-receptor-microbe-disease interaction network for human health that may form one of the key knowledge maps of precision medicine in the future.

In Silico Evaluation of the Antimicrobial Activity of Thymol-Major Compounds in the Essential Oil of Lippia thymoides Mart. & Schauer (Verbenaceae).

In this paper, we evaluated the drug-receptor interactions responsible for the antimicrobial activity of thymol, the major compound present in the essential oil (EO) of Lippia thymoides (L. thymoides) Mart. & Schauer (Verbenaceae). It was previously reported that this EO exhibits antimicrobial activity against Candida albicans (C. albicans), Staphylococcus aureus (S. aureus), and Escherichia coli (E. coli). Therefore, we used molecular docking, molecular dynamics simulations, and free energy calculations to investigate the interaction of thymol with pharmacological receptors of interest to combat these pathogens. We found that thymol interacted favorably with the active sites of the microorganisms’ molecular targets. MolDock Score results for systems formed with CYP51 (C. albicans), Dihydrofolate reductase (S. aureus), and Dihydropteroate synthase (E. coli) were −77.85, −67.53, and −60.88, respectively. Throughout the duration of the MD simulations, thymol continued interacting with the binding pocket of the molecular target of each microorganism. The van der Waals (ΔEvdW = −24.88, −26.44, −21.71 kcal/mol, respectively) and electrostatic interaction energies (ΔEele = −3.94, −11.07, −12.43 kcal/mol, respectively) and the nonpolar solvation energies (ΔGNP = −3.37, −3.25, −2.93 kcal/mol, respectively) were mainly responsible for the formation of complexes with CYP51 (C. albicans), Dihydrofolate reductase (S. aureus), and Dihydropteroate synthase (E. coli).

Covalent immobilization of beta2 adrenergic receptor through trans-methylation reaction by SNAP-tag and its application in anti-asthmatic compound screening from Raphani Semen

Beta2-adrenergic receptor (β2-AR) is believed as an attractive target for anti-asthmatic drugs. Its crystal structure and pharmacological activity have been clearly investigated. Yet the number of the approved anti-asthmatic drugs has declined in recent years. This work reports on the preparation of an immobilized β2-AR column through the specific trans-methylation reaction between SNAP tag and the benzyl-guanine derivative and application in anti-asthmatic compound screening from Raphani Semen. The characterization of the immobilized β2-AR was performed by scanning electron microscopy (SEM) and receptor-ligand interaction analysis by chromatographic methods. SEM analysis showed that the receptor has been successfully coated on the surface of PEGA amino microspheres. Binding constants of salbutamol and terbutaline calculated from frontal analysis within the temperature range of 10–30 ℃ confirmed the feasibility of the method in a thermodynamic viewpoint. Hydrogen bond was verified as the main driving force for drug-receptor interaction analysis. Sinapine was identified as the potential bioactive compound in Raphani Semen that specifically bind with β2-AR with a specific binding site of Ser 207. Taking together, the immobilized β2-AR column is promising in exploring drug-protein interaction analysis and anti-asthmatic drug screening.

A Piroxicam Inclusion Complexation for Solubility Enhancement: Design and Development

Published on:June 2022 Journal of Young Pharmacists, 2022; 14(2):192-197 Original Article | doi:10.5530/jyp.2022.14.36 Authors: Saravanakumar Kasimbedu1,*, Shilpaja Chella1, Bharathi T1, Nagaveni Pommala2, Durga Srinivasa Rao Mannepalli3 1Department of Pharmaceutics, Sree Vidyanikethan College of Pharmacy, Sree Sainath Nagar, Tirupati, Andhra Pradesh, INDIA. 2Department of Pharmaceutics, S.V.U. College of Pharmaceutical Sciences, S.V. University, Tirupati, Andhra Pradesh, INDIA.3Department of Pharmaceutics, Jagan’s Institute of Pharmaceutical Sciences, Muthukur, SPSR Nellore, Andhra Pradesh, INDIA. Abstract: Background: Over last few years, the physical and chemical characteristics of inclusion complexes have generated a lot of attention. One of the most important reasons for this is the significance of enzyme-substrate and drug-receptor interactions in inclusion complexes. Materials and Methods:The aim of the study was to design Piroxicam’s inclusion complexation, to improve its solubility by the reduction of particle size which leads to improve the particle surface area thereby increases the wettability of the mixture. Physical mixture, co-grinded mixture, kneading and solvent evaporation method were used to prepare the inclusion complexation of Piroxicam with β-cyclodextrin at 1:0.5, 1:1, and 1:2 w/w (Piroxicam/β-cyclodextrin) ratios. Results: Differential scanning calorimetry, Fourier-transform infrared and X-ray diffraction and scanning electron microscopy studies were used to investigate the interaction of Piroxicam with β-cyclodextrin. From scanning electron microscopic studies, it was observed that crystalline were formed as spherical in shape with rough surface, small piece and Pure Piroxicam in crystalline form with rough surfaces. From Scanning electron microscopic studies, it was observed that amorphous were formed as spherical in shape with smooth surface, wide piece and β-Cyclodextrine in amorphous form with rough surfaces. Conclusion: The inclusion complexations of Piroxicam with β-cyclodextrin exhibited higher saturation solubility and dissolution rate than that of the pure drug of Piroxicam. Formulation K2 showed more drug release rate by reducing the particle size with complexation technique like kneading technique.Keywords: Co-grinded mixture, Inclusion Complexation, Kneading, Wetting Property, Particle Shap