Formulation and Development of Fast Disintegrating Azelnidipine Tablets: Functionality of Superdisintegrants

Azelnidipine, a calcium channel blocker, is used for hypertension and angina pectoris. Azelnidipine fast-disintegrating tablets (FDT) have been prepared by kneading method. In the present study cyclodextrins (?CD and HP?CD) and surfactants (Kolliphor HS15) were tried to enhance the solubility and dissolution rate of Azelnidipine. The individual main effects and combined (interaction) effects of cyclodextrins and surfactants on the solubility and dissolution rate of Azelnidipine was evaluated in a series of 22 factorial experiments.) The hardness, friability, drug content and disintegration time, in vitro release and stability parameter has been studied. Hardness of the tablets was in the range 6.0 –7.5 kg/sq.cm. Percent weight loss in the friability test was less than 0.85% with all the formulations. The disintegration time was in the range 1 –3.5 min. with all the tablets prepared. Drug content of the tablets was within 100 ± 2% of the labeled claim. The dissolution efficiency was also increased from 4.56% for formulation E1 to 41.54 % and 36.59 % respectively for formulations E4 and E8. The formulation did not show any change in disintegration time and drug content after stability period. It was concluded that fast disintegrating Azelnidipine tablets can be prepared by kneading method using super disintegrants.

Enhanced solubility of Albendazole in Cyclodextrin Inclusion Complex: A Molecular Modeling Approach and Physicochemical Evaluation

Background: Albendazole (ABZ) is the drug of choice for the treatment of a variety of human and veterinary parasites. However, it has low aqueous solubility and low bioavailability. Cyclodextrins (CD) are pharmaceutical excipients with the ability to modulate the solubilization property of hydrophobic molecules. Objective: To analyze (Autodock Vina software and CycloMolder platform) the formation of inclusion complexes between ABZ, β-cyclodextrin (β-CD) and its derivatives, Methyl-β-cyclodextrin (M-β-CD) and Hydroxypropyl-β-cyclodextrin (HP-β-CD), through in vitro and in silico studies. Methods: The most stable inclusion complexes were produced by the kneading method and characterized by Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-Ray Diffraction (XRD), determination of the ABZ content, and in vitro dissolution profile. Results: Molecular modeling revealed that inclusion complexes between HP-β-CD:ABZ (in the proportion 1:1 and 2:1) presented the lowest formation energy and the highest number of intermolecular interactions, showing that the use of more cyclodextrins does not provide any gain in the stability of the complex. Through the characterization tests, the complexes experimentally obtained by kneading method demonstrated a highly suggestive method, including ABZ in HP-β-CD in both molar proportions; The results of this study showed suppression of bands in the infrared spectrum, displacement of the drug's melting temperature in DSC, crystallinity halos instead of the characteristic peaks of ABZ crystals in the XRD and a release of more than 80% of ABZ in less than 5 minutes, beyond dissolution efficiency of up to 92%. Conclusion: In silico studies provided a rational selection of the appropriate cyclodextrin, enabling the elaboration of more targeted complexes, decreasing time and costs to elaborate on new formulations that increase the oral biodisponibility of ABZ.

Pre-Fibrillation of Pulps to Manufacture Cellulose Nanofiber Reinforced High-Density Polyethylene using the Dry-Pulp Direct Kneading Method

The dry-pulp direct-kneading method is an industrially viable, low-energy process to manufacture cellulose nanofiber (CNF) reinforced polymer composites, where chemically modified pulps can be nanofibrillated and dispersed uniformly in the polymer matrix during melt-compounding. In this study, cellulose fibers with different sizes, ranging from surface-fibrillated pulps with 20 µm in width to fine CNFs with 20 nm in width were prepared from softwood bleached kraft pulps (NBKPs) using a refiner and high-pressure homogenizer (HPH). These cellulose fibers were modified with alkenyl succinic anhydride (ASA), and then dried. The dried ASA-treated cellulose fibers were used as a feed material for melt-compounding in the dry-pulp direct kneading method to fabricate CNF reinforced high-density polyethylene (HDPE). When surface-fibrillated pulps were employed as a feed material, the pulps were nanofibrillated and dispersed uniformly in the HDPE matrix during the melt-compounding, and the composites had much better properties (i.e., much higher tensile modulus and strength and much lower coefficient of thermal expansion) than the composites produced using the pulps without pre-fibrillation. However, when CNFs were used as a feed material, the CNFs were shortened and agglomerated during the melt-compounding, thus deteriorating the properties of the composites. The study concludes that the pre-fibrillation of pulps had a significant impact on the morphology and properties of the composites. Unexpectedly, the surface-fibrillated pulp, which can be produced cost-effectively using a refiner at an industry scale, was a more suitable form than the CNF as a feed material for melt-compounding in the dry-pulp direct kneading method.

Hybrid Liquisolid technique: A novel approach to enhance the in-vitro performance of antidiabetic drugs

Background: A combination of Glimepiride and Boswellia serrata extract reduces Neuropathic diabetic complications by reducing the peroxidase level and improving the antioxidant level. The hybrid Liquisolid method includes a combination of two methods, kneading and the Liquisolid method to enhance drug in-vitro performance. Objective: The objective of this study was to enhance the in-vitro performance of antidiabetics drugs. Method: Tablets of the fixed dose combination of Glimepiride and Boswellia serrata extract were formulated by kneading method followed by Liquisolid method. Screening of non-volatile solvents, carriers, and coating materials was performed. The design of the experiment was applied to optimize the formulation and validation was done to validate the obtained model from the design of the experiment. 3 level 2 factorial (32) Design was applied by using Design expert software 11. Various pre-compression parameters were performed to check the quality of the formulation. Results: Screening of excipients for kneading method, Glimepiride with PVP K 30 (5%), and Boswellia serrata extract with Poloxamer 188 (13%) give optimum drug release. For the Liquisolid method Propylene glycol: PEG 400: Tween 80 (1:2:4) ratio for Glimepiride and PEG 400: Tween 80 (1:3) ratio for Boswellia serrata extract were selected. Common carrier and coating material for both drug Syloid XDP 3150: Aeroperl 300 (3:1) ratio were selected, which improves the in-vitro performance of the drug. Conclusion: This study gives an overall understanding of the impact of excipients on the quality of formulation, a critical knowledge to the implementation of this kind of novel application of Liquisolid systems.

Formulation and Development of Fast Disintegrating Efonidipine Tablets: Functionality of Superdisintegrants

Efnodipine, a calcium channel blocker, is used for hypertension and angina pectoris. Efnodipine fast-disintegrating tablets (FDT) have been prepared by kneading method. In the present study cyclodextrins (?CD and HP?CD) and surfactants (Kolliphor HS15) were tried to enhance the solubility and dissolution rate of Efnodipine. The individual main effects and combined (interaction) effects of cyclodextrins and surfactants on the solubility and dissolution rate of Efnodipine was evaluated in a series of 22 factorial experiments.) The hardness, friability, drug content and disintegration time, in vitro release and stability parameter has been studied. Hardness of the tablets was in the range 6.0 –7.5 kg/sq.cm. Percent weight loss in the friability test was less than 0.85% with all the formulations. The disintegration time was in the range 1 –3.5 min. with all the tablets prepared. Drug content of the tablets was within100 ± 2% of the labeled claim. The dissolution efficiency was also increased from 4.56% for formulation E1 to 41.54 % and 36.59 % respectively for formulations E4 and E8. The formulation did not show any change in disintegration time and drug content after stability period. It was concluded that fast disintegrating Efnodipine tablets can be prepared by kneading method using super disintegrants.

Inclusion Complex of Iloperidone with Sulfobutyl Ether Beta-Cyclodextrin: Characterization and Dissolution Studies

Iloperidone (ILO) is a second-generation antipsychotic drug and a first-line treatment approved by USFDA in May 2009. Iloperidone belongs to Biopharmaceutical Classification Systems (BCS) class II; thus, it is poorly water-soluble, highly permeable, and has pH-dependent solubility. Cyclodextrins and their derivatives have a wide range of applications in different formulations due to their complexation ability, which improves the solubility, stability, safety, and bioavailability of a drug. We have tried the complexation of iloperidone with sulfobutyl ether-β-cyclodextrin (SEβCD) to improve its solubility and dissolution. Complexation was done by the kneading method. The characterization of the SEβCD complexes with Iloperidone was done by FTIR, differential scanning calorimetry (DSC), saturation solubility, etc. A multimedia dissolution of the complex was carried out and compared with the plain drug. A significant improvement in drug release was found from SEβCD complexes in all media when compared with the drug alone.

Encapsulation of the Natural Product Tyrosol in Carbohydrate Nanosystems and Study of Their Binding with ctDNA

Tyrosol, a natural product present in olive oil and white wine, possesses a wide range of bioactivity. The aim of this study was to optimize the preparation of nanosystems encapsulating tyrosol in carbohydrate matrices and the investigation of their ability to bind with DNA. The first encapsulation matrix of choice was chitosan using the ionic gelation method. The second matrix was β-cyclodextrin (βCD) using the kneading method. Coating of the tyrosol-βCD ICs with chitosan resulted in a third nanosystem with very interesting properties. Optimal preparation parameters of each nanosystem were obtained through two three-factor, three-level Box-Behnken experimental designs and statistical analysis of the results. Thereafter, the nanoparticles were evaluated for their physical and thermal characteristics using several techniques (DLS, NMR, FT-IR, DSC, TGA). The study was completed with the investigation of the impact of the encapsulation on the ability of tyrosol to bind to calf thymus DNA. The results revealed that tyrosol and all the studied systems bind to the minor groove of ctDNA. Tyrosol interacts with ctDNA via hydrogen bond formation, as predicted via molecular modeling studies and corroborated by the experiments. The tyrosol-chitosan nanosystem does not show any binding to ctDNA whereas the βCD inclusion complex shows analogous interaction with that of free tyrosol.

Enhancement of solubility and dissolution rate of ebastine fast-disintegrating tablets by solid dispersion method

Purpose: To investigate the efficiency of different solubilizing agents in improving solubility as well as dissolution rate of ebastine (a BCS class II drug) by incorporating prepared solid dispersion into fast disintegrating tablets.Method: The solubility of ebastine was determined in distilled water, lipids and solubilizing agents. Subsequently, the binary solid dispersions were prepared by kneading method using varying weight ratios of ebastine and solubilizing agents. The solid dispersions were then incorporated into fast disintegrating tablets (SD-FDT). Central composite rotatable design (CCD) was used to determine the impact of super disintegrating agents on disintegration time and friability of tablets. The solubility and dissolution rate of developed SD-FDT were compared with a marketed brand. The solid dispersion particles were characterized by Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder x-ray diffraction (P-XRD) and scanning electron microscopy (SEM).Results: The saturated solubility of pure ebastine in water was 0.002 ± 0.041 mg/ml while the aqueous solubility of EBT/poloxamer solid dispersion SET3 (P) was 0.018 ± 2.510 mg/ml; on the other hand, EBT/soluplus solid dispersion SET1(S) has an aqueous solubility of 0.242 ± 1.390 mg/ml. Within 30 min, drug release was 14.00 ± 1.77, 78.00 ± 2.31 and 98.70 ± 2.54 % from pure EBT, SET3 (P) and SET1(S), respectively.Conclusion: The solubility and dissolution rate of ebastine has been successfully enhanced by incorporating its solid dispersion in fast-disintegrating tablets (SD-FDT). Keywords: Ebastine, Solid dispersion, Poloxamer 188, Soluplus, Solubility, Dissolution

Effect of Hydrophilic Polymers on Complexation Efficiency of Cyclodextrins in Enhancing Solubility and Release of Diflunisal

The effects of three hydrophilic polymers, namely, carboxymethyl cellulose sodium (CMC-Na), polyvinyl alcohol (PVA) and poloxamer-188 (PXM-188) on the solubility and dissolution of diflunisal (DIF) in complexation with β-cyclodextrin (βCD) or hydroxypropyl β-cyclodextrin (HPβCD), were investigated. The kneading method was used at different drug to cyclodextrin weight ratios. Increases in solubility and drug release were observed with the DIF/βCD and DIF/HPβCD complexes. The addition of hydrophilic polymers at 2.5, 5.0 and 10.0% w/w markedly improved the complexation and solubilizing efficiency of βCD and HPβCD. Fourier-transform infrared (FTIR) showed that DIF was successfully included into the cyclodextrin cavity. Differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) confirmed stronger drug amorphization and entrapment in the molecular cage of cyclodextrins. The addition of PVA, CMC-Na or PXM-188 reduced further the intensity of the DIF endothermic peak. Most of the sharp and intense peaks of DIF disappeared with the addition of hydrophilic polymers. In conclusion, PXM-188 at a weight ratio of 10.0% w/w was the best candidate in enhancing the solubility, stability and release of DIF.

Solid Dispersion (Kneading) Technique: A Platform for Enhancement Dissolution Rate of Valsartan Poorly Water Soluble Drug

The objective of this study was to the enhancement of dissolution rate of Valsartan. Using a solid dispersion (kneading) method with Kollidon and Povidone K30 as a carrier. Eight different drugs: Carrier ratios were prepared. Using factorial design taking 3 factors i.e., the concentration of Valsartan (x1), Kollidon (x2), and Povidone K30(x3). The enhancement of dissolution depends on the amount of carrier and an increase in the concentration of carrier. Enhancement of dissolution rate depends on reduce particle size of drug place on the surface of carrier and increased wettability of drug particle by carrier. Solid Dispersions prepared with Kollidon as a carrier in ratio 1:4 shows the enhancing dissolution in 30 mins to drug and Physical Mixture. Formulation evaluated by fourier-transform infrared spectroscopy, differential scanning colorimetry, X-ray diffraction, Scanning Electron Microscopy.