scholarly journals Amorphisation of Free Acid Ibuprofen and Other Profens in Mixtures with Nanocellulose: Dry Powder Formulation Strategy for Enhanced Solubility

Pharmaceutics ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 68 ◽  
Author(s):  
Athanasios Mantas ◽  
Valentine Labbe ◽  
Irena Loryan ◽  
Albert Mihranyan
Keyword(s):  
Surface Area ◽  
Free Acid ◽  
High Surface ◽  
In Vitro Dissolution ◽  
Pharmacokinetic Analysis ◽  
Strong Impact ◽  
Scanning Calorimetry ◽  
Biorelevant Media ◽  
Enhanced Solubility

The formulation of arylpropionic acid derivatives (profens), which are poorly soluble Biopharmaceutical Classification System (BCS) Type II drugs, has a strong impact on their therapeutic action. This article shows that heat-treated powder mixtures of free acid profens with high surface area Cladophora cellulose induces drug amorphization and results in enhanced solubility and bioavailability. Similar mixtures produced using conventional low surface area cellulose, i.e., microcrystalline cellulose, does not produce the same effect. The concept is thoroughly described and links the solid-state characterization data, such as differential scanning calorimetry, X-ray powder diffraction, and Fourier-transform infra-red spectroscopy, with in vitro dissolution in biorelevant media and in vivo pharmacokinetic analysis in rats. The concept is demonstrated for several substances from the profens group, including ibuprofen (main model drug), ketoprofen, flurbiprofen, and naproxen. The presented approach opens new ways to produce solid dosage forms of profen drugs in their free acidic form as alternatives to existing analogues, e.g., drug-salt conjugates or soft gel liquid capsules.

scholarly journals Directly Compressed Tablets of Free Acid Ibuprofen with Nanocellulose Featuring Enhanced Dissolution: A Side-by-Side Comparison with Commercial Oral Dosage Forms

Pharmaceutics ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 71 ◽  
Author(s):  
Athanasios Mantas ◽  
Marie-Amélie Petit ◽  
Albert Mihranyan
Keyword(s):  
Surface Area ◽  
Free Acid ◽  
High Surface ◽  
High Surface Area ◽  
Oral Dosage ◽  
Simulated Gastric Fluid ◽  
Intestinal Fluid ◽  
Biorelevant Media ◽  
Simulated Intestinal Fluid ◽  
Enhanced Dissolution

We have previously reported that heated powder mixtures of ibuprofen (IBU) and high surface area nanocellulose exhibit an enhanced dissolution and solubility of the drug due to IBU amorphization. The goal of the present work was to further elaborate the concept and conduct side-by-side in vitro drug release comparisons with commercial formulations, including film-coated tablets, soft gel liquid capsules, and IBU-lysine conjugate tablets, in biorelevant media. Directly compressed tablets were produced from heated mixtures of 20% w/w IBU and high surface area Cladophora cellulose (CLAD), with 5% w/w sodium croscarmelose (AcDiSol) as superdisintegrant. The side-by side studies in simulated gastric fluid, fasted-state simulated intestinal fluid, and fed-state simulated intestinal fluid corroborate that the IBU-CLAD tablets show more rapid and less variable release in various media compared to three commercial IBU formulations. On the sidelines of the main work, a possibility of the presence of a new meta-crystalline form of IBU in mixture with nanocellulose is discussed.

scholarly journals Effect of inclusion of citric acid and Lutrol® F-68 on ziprasidone and β-cyclodextrin complexation: Characterization, solubility and dissolution studies

2020 ◽  
Vol 11 (4) ◽  
pp. 280-284
Author(s):  
Vaishali Yogesh Londhe ◽  
Sreevidya Ramesh Krishnan
Keyword(s):  
Citric Acid ◽  
Antipsychotic Agent ◽  
Aqueous Solubility ◽  
In Vitro Dissolution ◽  
Scanning Calorimetry ◽  
Solubility Study ◽  
Dissolution Studies ◽  
Enhanced Solubility ◽  
Ft Ir

Ziprasidone (ZPR) is an antipsychotic agent having less solubility. It is used for the treatment of schizophrenia. Complexation of hydrophobic drugs with cyclodextrins leads to enhanced solubility and dissolution. In this study, inclusion complexes were prepared by different methods, using ZPR, β-cyclodextrin (β-CD), and different auxiliary agents like hydrophilic polymer and hydroxy acid (1:1:0.5) to improve the aqueous solubility. The characterization of the ternary complexes was carried out using solubility study, Differential scanning calorimetry (DSC), Powder X-ray diffraction (PXRD), Fourier transformation infrared spectroscopy (FT-IR) and in vitro dissolution studies. DSC, XRD, and FT-IR studies showed interaction in drug, cyclodextrin, and auxiliary agents which are confirmed by enhancement of solubility and dissolution. Spray-dried dispersion showed less crystallinity and higher solubility as compared to the kneading method for both citric acid and Lutrol® F-68. Thus, the investigation concludes that the presence of the auxiliary agent has a synergistic action on complexation with cyclodextrin, which helps to modify the physicochemical properties of the drug.

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

2021 ◽  
Vol 18 ◽  
Author(s):  
Camila Gomes de Melo ◽  
Lucas Amadeu Costa Gonzaga ◽  
Marcelo Montenegro Rabello ◽  
Victor de Albuquerque Wanderley Sales ◽  
Aline Silva Ferreira ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Inclusion Complexes ◽  
In Silico ◽  
In Vitro Dissolution ◽  
Dissolution Profile ◽  
Scanning Calorimetry ◽  
Kneading Method ◽  
In Silico Studies ◽  
Enhanced Solubility

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.

The Potential Migrated Mechanism of Water-Soluble Components in Pellets Prepared by Wet Extrusion/Spheronization: Effect of Drying Rate

2020 ◽  
Vol 17 ◽  
Author(s):  
Bingwei Wang ◽  
Jianping Liu ◽  
Zhenghua Li ◽  
Yulong Xia ◽  
Shuangshuang Zhang ◽  
...  
Keyword(s):  
Relative Humidity ◽  
Water Soluble ◽  
In Vitro Dissolution ◽  
Drying Rate ◽  
Scanning Calorimetry ◽  
Drying Temperature ◽  
Wet Extrusion ◽  
Extrusion Spheronization ◽  
Soluble Components

Background: At present, there were numerous researches on the migration of components in tablets and granules, the investigation in the pharmaceutical literatrue concerning the effect of drying rate on the migration of water-soluble components of pellets was limited. Temperature and relative humidity (RH) were crucial parameters during the drying process which was an essential step in the preparation of pellets via wet extrusion/spheronization. To quantify these variables, the water loss percentage of pellets per minute was defined as drying rate. Objective: The study aimed to investigate the influence of drying rate on the migration of water-soluble components in wet pellets and the potential migrated mechanism. Methods: The pellets containing tartrazine as a water-soluble model drug and microcrystalline cellulose as a matrix former were prepared by extrusion/spheronization and dried at four different drying temperature and relative humidity. Afterward, the extent of migrated tartrazine was assessed regarding appearance, in-vitro dissolution test, Differential Scanning Calorimetry, X-Ray Powder Diffraction, Attenuated total reflectance Fourier transform infrared spectroscopy and Confocal Raman Mapping. Results: Results demonstrated that red spots of tartrazine appeared on the surface of pellets and more than 40% tartrazine were burst released within 5 minutes when pellets dried at 60℃/RH 10%. While pellets dried at 40℃/RH 80%, none of these aforementioned phenomena was observed. Conclusion: In conclusion, the faster drying rate was, the more tartrazine migrated to the exterior of pellets. Adjusting drying temperature and relative humidity appropriately could inhibit the migration of water-soluble components within wet extrusion/spheronization pellets.

Smart Gn-Keto Nanohybrid Embedded Topical System for Effective Management of Dermatophytosis

2019 ◽  
Vol 9 (1) ◽  
pp. 21-28
Author(s):  
Nisha Sharma ◽  
Shashikiran Misra
Keyword(s):  
Antifungal Activity ◽  
Fungal Infections ◽  
High Surface ◽  
High Surface Area ◽  
Vital Role ◽  
Common Disease ◽  
Microdilution Method ◽  
Enhanced Solubility ◽  
Bioactive Agents

Background and Objectives: Dermatophytosis (topical fungal infection) is the 4th common disease in the last decade, affecting 20-25% world’s population. Patients of AIDS, cancer, old age senescence, diabetes, cystic fibrosis become more vulnerable to dermatophytosis. The conventional topical dosage proves effective as prophylactic in preliminary stage. In the advanced stage, the therapeutics interacts with healthy tissues before reaching the pathogen site, showing undesirable effects, thus resulting in pitiable patient compliance. The youngest carbon nano-trope “Graphene” is recently used to manipulate bioactive agents for therapeutic purposes. Here, we explore graphene via smart engineering by virtue of high surface area and high payload for therapeutics and developed graphene–ketoconazole nanohybrid (Gn-keto) for potent efficacy towards dermatophytes in a controlled manner. </P><P> Methods: Polymethacrylate derivative Eudragit (ERL100 and ERS 100) microspheres embedded with keto and Gn-keto nanohybrid were formulated and characterized through FTIR, TGA, and SEM. In vitro drug release and antifungal activity of formulated Gn-keto microspheres were assessed for controlled release and better efficacy against selected dermatophytes. </P><P> Results: Presence of numerous pores within the surface of ERL100 microspheres advocated enhanced solubility and diffusion at the site of action. Controlled diffusion across the dialysis membrane was observed with ERS100 microspheres owing to the nonporous surface and poor permeability. Antifungal activity against T. rubrum and M. canis using microdilution method focused on a preeminent activity (99.785 % growth inhibition) of developed nanohybrid loaded microspheres as compared to 80.876% of keto loaded microspheres for T. rubrum. The culture of M. canis was found to be less susceptible to formulated microspheres. Conclusion: Synergistic antifungal activity was achieved by nanohybrid Gn-Keto loaded microspheres against selected topical fungal infections suggesting a vital role of graphene towards fungi.

scholarly journals DESIGN, OPTIMIZATION AND EVALUATION OF CETRIZINE DIHYDROCHLORIDE FAST DISSOLVING FILMS EMPLOYING STARCH TARTRATE–A NOVEL SUPERDISINTEGRANT

2019 ◽  
pp. 75-86
Author(s):  
R. SANTOSH KUMAR ◽  
ANNU KUMARI ◽  
B. KUSUMA LATHA ◽  
PRUDHVI RAJ
Keyword(s):  
Tensile Strength ◽  
Drug Dissolution ◽  
In Vitro Dissolution ◽  
Content Uniformity ◽  
Scanning Calorimetry ◽  
Disintegration Time ◽  
Folding Endurance ◽  
Contour Plots ◽  
The Individual

Objective: The aim of the current research is optimization, preparation and evaluation of starch tartrate (novel super disintegrant) and preparation of fast dissolving oral films of cetirizine dihydrochloride by employing starch tartrate. Methods: To check the drug excipient compatibility studies of the selected drug (Cetrizine dihydrochloride) and the prepared excipient i. e starch tartrate, different studies like FTIR (Fourier-transform infrared spectroscopy), DSC (Differential scanning calorimetry) and thin-layer chromatography (TLC) were carried out to find out whether there is any interaction between cetirizine dihydrochloride and starch tartrate. The solvent casting method was used for the preparation of fast dissolving films. The prepared films were then evaluated for thickness, folding endurance, content uniformity, tensile strength, percent elongation, in vitro disintegration time and in-vitro dissolution studies. Response surface plots and contour plots were also plotted to know the individual and combined effect of starch tartrate (A), croscarmellose sodium (B) and crospovidone (C) on disintegration time and drug dissolution efficiency in 10 min (dependent variables). Results: Films of all the formulations are of good quality, smooth and elegant by appearance. Drug content (100±5%), thickness (0.059 mm to 0.061 mm), the weight of films varies from 51.33 to 58.06 mg, folding endurance (52 to 67 times), tensile strength (10.25 to 12.08 N/mm2). Fast dissolving films were found to disintegrate between 34 to 69 sec. Percent dissolved in 5 min were found to be more in F1 formulation which confirms that starch tartrate was effective at 1%. Conclusion: From the research conducted, it was proved that starch tartrate can be used in the formulation of fast dissolving films of cetirizine dihydrochloride. The disintegration time of the films was increased with increase in concentration of super disintegrant.

Formulation and Evaluation of Benidipine Nanosuspension

2021 ◽  
pp. 4111-4116
Author(s):  
Sejal Patel ◽  
Anita P. Patel
Keyword(s):  
Particle Size ◽  
Water Solubility ◽  
Polymer Concentration ◽  
Oral Route ◽  
Water Soluble ◽  
In Vitro Dissolution ◽  
Scanning Calorimetry ◽  
23 Factorial Design ◽  
Selection Of

In the interest of administration of dosage form oral route is most desirable and preferred method. After oral administration to get maximum therapeutic effect, major challenge is their water solubility. Water insoluble drug indicate insufficient bioavailability as well dissolution resulting in fluctuating plasma level. Benidipine (BND) is poorly water soluble antihypertensive drug has lower bioavailability. To improve bioavailability of Benidipine HCL, BND nanosuspension was formulated using media milling technique. HPMC E5 was used to stabilize nanosuspension. The effect of different important process parameters e.g. selection of polymer concentration X1(1.25 mg), stirring time X2 (800 rpm), selection of zirconium beads size X3 (0.4mm) were investigated by 23 factorial design to accomplish desired particle size and saturation solubility. The optimized batch had 408 nm particle size Y1, and showed in-vitro dissolution Y2 95±0.26 % in 30 mins and Zeta potential was -19.6. Differential scanning calorimetry (DSC) and FT-IR analysis was done to confirm there was no interaction between drug and polymer.

scholarly journals PREPARATION AND CHARACTERIZATION OF NANOCRYSTALS FOR SOLUBILITY AND DISSOLUTION RATE ENHANCEMENT OF PALIPERIDONE USING DIFFERENT HYDROPHILIC CARRIERS: IN VITRO-IN VIVO STUDY

2018 ◽  
Vol 11 (4) ◽  
pp. 393
Author(s):  
Moon Rajkumar ◽  
Gattani Surendra
Keyword(s):  
Dissolution Rate ◽  
Antipsychotic Agent ◽  
Aqueous Solubility ◽  
In Vivo Study ◽  
Scanning Calorimetry ◽  
Antisolvent Precipitation ◽  
Enhanced Solubility ◽  
Pure Drug

 Objective: The objective of this study was to increase the solubility and dissolution rate of paliperidone (PAL) by preparing its nanocrystals using different hydrophilic carriers by antisolvent precipitation technique.Methods: The nanoparticles (NP) were characterized for aqueous solubility, drug content, Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, particle size, and in vitro-in vivo analysis.Results: The results showed improved solubility and dissolution rate of NPs when compared to pure drug and physical mixture (PM). Solubility data showed a linear graph giving an indication that there is a gradual increase in the solubility profile of the drug with an increase in concentration of the carriers. At highest concentration, the solubility of NPs with Plasdone S630, Povidone K-25, and PVP K-30 found to be increased by 12 folds, 9 folds and 6 folds, respectively, as compared to pure drug. The release profile of NPs with Plasdone S630 in terms of dissolution efficiency at 60 min (DE60), initial dissolution rate (IDR), amount release in 15 min (Q15 min), and time for 75% release (t75%) shows better results when compared to pure drug, PM, and also NPs with povidone 25 and povidone 30. In vivo study reveals that optimized NPs elicited significant induction of cataleptic behavior which is the indication of antipsychotic agent(s) effect.Conclusion: The process antisolvent precipitation under constant stirring may be a promising method to produce stable PAL NPs with markedly enhanced solubility and dissolution rate due to nanonization with the increased surface area, improved wettability, and reduced diffusion pathway.

scholarly journals A New Zinc-based Metal Organic Framework as a Stationary Phase for Thin Layer Chromatography

2020 ◽  
pp. 107-117
Author(s):  
Mouhammad Abu Rasheed ◽  
Ahmad Alshaghel ◽  
Amir Alhaj Sakur
Keyword(s):  
Thin Layer ◽  
Stationary Phase ◽  
Thin Layer Chromatography ◽  
Surface Area ◽  
High Surface ◽  
Ultra Sound ◽  
Diffuse Reflection Spectroscopy ◽  
Scanning Calorimetry ◽  
Metal Organic ◽  
Layer Chromatography

Metal organic frameworks (MOFs) are a variety of micro-porous materials which have high surface area, and permanent porosity making them possible options as chromatographic stationary phases. Herein we reported the synthesis and characterization of a new MOF structure and its utilization as a stationary phase for thin layer chromatography (TLC). [Zn(BMAB).DMF]n is a zinc-based MOF with an organic linker consists of chemically distinct binding groups which is 4-{[(1h-1,2,3-benzotriazol-1-yl)methyl]amino}benzoic acid (BMAB). This MOF was synthesized using ultra sound assisted reaction process, then activated via solvent exchange protocol to preserve its porous structure. FT-IR, UV-diffuse reflection spectroscopy (UV-DRS) and differential scanning calorimetry (DSC) were performed to characterize the synthesized MOF. Integrated data from "loss on desolvation" and atomic absorption spectrophotometry (AAS) measurements were used to define the chemical composition of the synthesized material. A specific surface area of 122.9 m2/g was determined for the activated MOF using methylene blue langmuir isotherm method. TLC plates were prepared from the activated form of the structure to investigate its chromatographic characteristics by utilizing it to separate a model mixture of benzidine and o-tolidine using n-propanol: Chloroform: Acetonitrile (50:30:20, v/v/v) as a mobile phase. The retardation factors (Rf), separation factor, and resolution (Rs) were determined via densitometric method at 310 nm to be 0.45 and 0.63 (α=2.08, Rs=1.61) for o-tolidine and benzidine; respectively. The plate was then visualized using iodine chamber method to confirm a successful separation.

EFFECT OF DRUG TO B-CYCLODEXTRIN RATIO AND METHOD OF COMPLEXATION IN THE DEVELOPMENT OF B-CYCLODEXTRIN INCLUSION COMPLEX OF OFLOXACIN

INDIAN DRUGS ◽  
2013 ◽  
Vol 50 (12) ◽  
pp. 34-40
Author(s):  
M Panchpuri ◽  
◽  
D Singh ◽  
A Semalty ◽  
M. Semalty
Keyword(s):  
Inclusion Complex ◽  
In Vitro Dissolution ◽  
Molar Ratio ◽  
Dissolution Profile ◽  
Scanning Calorimetry ◽  
Dissolution Study ◽  
Drug Content ◽  
Kneading Method ◽  
Made In

Ofloxacin, a second generation fluoroquinolone, shows poor aqueous solubility and dissolution profile. Thus, ofloxacin–β-cyclodextrin complexes were prepared to improve its dissolution by imparting an environment of improved hydrophilicity. Ofloxacin was complexed with β-cyclodextrin (in 1:1 and 1:2 molar ratio) by two different methods namely, solvent evaporation and kneading method. These inclusion complexes were evaluated for solubility, drug content, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X ray powder diffraction (XRPD) and in vitro dissolution study. The highest drug content (35.45%) was found in complex made by kneading method (OK1:1) in 1:1 molar ratio. All the complexes OSE1:1, OSE1:2, OK1:1, OK1:2 were found to be showing rough and porous surface morphology in SEM. Solubility as well as the dissolution of the complexes was found to be improved. Complex prepared by kneading method in 1:1 molar ratio (OK1:1) showed a marked improvement in percent drug release (88.94%) than that of pure drug (54.22%) at the end of 1 hour in dissolution study. FTIR, DSC and XRPD data confirmed the formation of inclusion complex. It was concluded that the complex made in 1:1 molar ratio (irrespective of the method) showed better solubility and dissolution profile as compared to complex made in 1:2 molar ratio.

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