Design of Experiment Approach to Assess The Effect Of Formulation Variables On Extrusion And Spheronization Of Telmisartan And Cilostazol Loaded Pellets And Its Pharmacokinetic Study

2021 ◽  
Vol 16 ◽  
Author(s):  
Kalpana Patel ◽  
Prutha Godhani ◽  
Hemangini Patel ◽  
Vaishali Thakkar ◽  
Tejal Gandhi ◽  
...  
Keyword(s):  
Inclusion Complex ◽  
Solid Dispersion ◽  
Pharmacokinetic Study ◽  
Class Ii ◽  
Phase Solubility ◽  
Solubility Study ◽  
Drug Content ◽  
Bcs Class Ii ◽  
Apparent Solubility ◽  
Phase Solubility Study

Background: Solubility is an important parameter that affects availability of drug in systemic circulation. Drugs having poor solubility belonging to BCS class II eventually results in lower dissolution and bioavailability. Hence, improvement of solubility is a challenging task. Hence the present work focusses on using solid dispersion and inclusion complex approach for both telmisartan and cilostazol belonging to BCS Class II drugs. Objective: The present study was carried out to improve apparent solubility of telmisartan and cilostazol (BCS-Class II drugs) and optimization as pellets along with its pharmacokinetic study. Methods: Phase solubility study was carried out to screen the excipients such as, PVPK30, PVA, HPMC E5 and β-CD. Solvent evaporation method was adopted to prepare the solid dispersions and inclusion complex of both the drugs. Pellets were optimized by extrusion spheronization method using 32 factorial design and characterized by morphology, drug content, DSC, FTIR, XRD, SEM, in-vitro studies and drug content study Results: Phase solubility study showed improved apparent solubility of telmisartan with HPMC E5 (1:3) by solid dispersion and cilostazol with β-CD (1:3) using inclusion complexation method. Drug characterization did not reveal any incompatibility. Formulation was optimized on the basis of acceptable pellet properties, including acceptable spherical shape and micromeritics properties. The percent friability of all batches was found to be less than 1%. The optimized pellets of both drugs prepared with micro crystalline cellulose provided desirable maximum release with acceptable release profile. Conclusion: The formulated pellets when studied in vivo showed superior pharmacokinetic profile. The drawback associated with apparent solubility and bioavailability of both drugs can thus be alleviated by use of novel pellet formulation.

BEHAVIOURAL STUDY OF CYCLODEXTRIN INCLUSION COMPLEX ON ENHANCEMENT OF SOLUBILITY OF ACECLOFENAC

INDIAN DRUGS ◽  
2015 ◽  
Vol 52 (11) ◽  
pp. 19-23
Author(s):  
J Shaikh ◽  
◽  
S. V. Deshmane ◽  
R. N Purohit ◽  
K. R. Biyani
Keyword(s):  
Inclusion Complex ◽  
Solid Dispersion ◽  
Water Soluble ◽  
In Vitro Dissolution ◽  
Phase Solubility ◽  
Solubility Study ◽  
Cyclodextrin Inclusion ◽  
Poorly Water Soluble ◽  
Cyclodextrin Inclusion Complex

The main objective of the present study was to enhance the solubility and dissolution rate of poorly water soluble aceclofenac using its solid dispersion with β-cyclodextrin. FTIR and DSC study was carried out to find out any incompatibility. The phase solubility of drug was carried out in 1, 2, 5, and 10% of β-cyclodextrin in distilled water. Kneading method and solvent evaporation method was use to prepared solid dispersion of aceclofenac and β-cyclodextrin. Different evaluation tests like solubility study in different solvents, PXRD and in vitro dissolution study of aceclofenac- β-cyclodextrin inclusion complex were carried out. The overall finding indicated that β-cyclodextrin is a desirable water soluble carrier, that helps in increasing solubility of drug. Due to its structural feature, β-cyclodextrin forms a good inclusion complex that decreases contact angle of drug with water molecules by increasing wetting properties. Hence, it can be concluded that, β-cyclodextrin is better water soluble carrier molecule in terms of its compatibility and increasing solubility behavior of poorly water soluble drug aceclofenac.

scholarly journals Dissolution Enhancement of Flurbiprofen by Solid Dispersion Adsorbate Technique

2021 ◽  
Vol 69 (2) ◽  
Author(s):  
Sohansinh S. Vaghela ◽  
Samkit M. Shah ◽  
Sanjesh G. Rathi ◽  
Shrenik K. Shah
Keyword(s):  
Solid Dispersion ◽  
Aqueous Solubility ◽  
Dissolution Enhancement ◽  
Phase Solubility ◽  
Fusion Method ◽  
Poloxamer 188 ◽  
X Ray ◽  
Solubility Study ◽  
Phase Solubility Study

Flurbiprofen solid dispersion Adsorbate (SDA) has been prepared using PEG 4000 and Poloxamer 188 as carrier and Neusilin as adsorbent material. The SDA of Flurbiprofen was prepared by using Fusion method in various drugs to carrier ratios. The phase solubility study concludes that both polymers have ability to improve the aqueous solubility of flurbiprofen. Pure API Flurbiprofen and final formulation samples of SDA are characterized by FTIR, DSC and X-ray diffraction spectroscopy. X-ray powder diffraction and DSC study indicated that the drug was present in amorphous form. FTIR study revealed that the characteristic peaks in spectra of pure Flurbiprofen are also present in spectra of SDA’s. Drug found compatible with the excipients. The highest improvement in solubility and in-vitro drug release were observed in solid dispersion prepared with Poloxamer 188 (F14) by fusion method. The increased dissolution rate of drug from solid dispersion adsorbates may be due to surface tension lowering effect of polymer to the medium and increased wettability and dispersibility of drug. Hence, F14 Solid dispersion adsorbates with the Poloxamer carrier in 1:2 ratio considered as most satisfactory among all solid dispersion adsorbates.

scholarly journals FORMULATION DEVELOPMENT AND EVALUATION OF GASTRO-RETENTIVE DOSAGE FORM OF ATAZANAVIR SULPHATE

2018 ◽  
Vol 10 (1) ◽  
pp. 60
Author(s):  
Hemant Kumar Jain ◽  
Madhuri Taware
Keyword(s):  
Solid Dispersion ◽  
Dosage Form ◽  
In Vitro Release ◽  
Hplc Method ◽  
Phase Solubility ◽  
Dissolution Profile ◽  
Formulation Development ◽  
Peg 6000 ◽  
Phase Solubility Study ◽  
Gastro Retentive

Objective: To improve dissolution properties of atazanavir sulphate by preparing gastro-retentive granules by solid dispersion method and development of RP-HPLC method for estimation of this drug.Methods: Estimation of atazanavir sulphate was done using high performance liquid chromatography (HPLC) on inertsil column (5 µm, 250x4, 6 mm) with a mobile phase consists of methanol: water (91:9 v/v), at 0.5 ml/min flow rate and 249 nm UV detection. The method was validated as per ICH guidelines. Selection of the carrier for gastro-retentive formulation was based on phase solubility study of the drug. Solid dispersions of gastro-retentive granules of different composition of drug and carrier, were prepared by the kneading, heating and solvent evaporation. A 32factorial design was applied to optimize the gastro-retentive formulation. The amounts of polyethylene glycol 6000 (PEG 6000) (X1) and hydroxypropyl methyl cellulose (HPMC) (X2) were selected as independent variables and in vitro-release at 5, 9 h and total floating time was selected as dependent variables. Results: HPLC method was found to be linear in a concentration range of 10-60 μg/ml of the drug (r2= 0.999). The low value of % RSD in precision study indicates reproducibility of the method. The low value of LOD and LOQ suggests the sensitivity of the method. The solubility enhancement study of drug with various carriers followed descending order of solubility [Gelucire 44/14>PEG 6000>polyvinyl pyrrilidone (PVP)]. Highest % cumulative release was observed for the heating method at drug polymer (PEG 6000) ratio 1:5. Hence, this ratio has been selected for preparation of solid dispersion. From comparison of dissolution profile of formulated batches, formulation F4 [containing PEG6000 (1.6 g) and HPMC (200 mg)] showed promising dissolution parameters with desired floating properties.Conclusion: Results obtained by validation studies suggested that the developed HPLC method is simple, accurate, precise and can be used for routine analysis of atazanavir sulphate formulation. Results of evaluation of prepared batches indicate that batch F4 is a promising formulation for gastro-retentive dosage form of drug. 

scholarly journals Enhanced Solubility, Stability, and Herbicidal Activity of the Herbicide Diuron by Complex Formation with β-Cyclodextrin

Polymers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1396 ◽  
Author(s):  
Shuang Gao ◽  
Jing-Yu Jiang ◽  
Yan-Yan Liu ◽  
Ying Fu ◽  
Li-Xia Zhao ◽  
...  
Keyword(s):  
Inclusion Complex ◽  
1H Nmr ◽  
Water Solubility ◽  
Herbicidal Activity ◽  
Environmental Damage ◽  
Phase Solubility ◽  
Scanning Calorimetry ◽  
Enhanced Solubility ◽  
Phase Solubility Study ◽  
Herbicide Diuron

The herbicide diuron is hardly soluble in water and most organic solvents and is usually made into a wettable powder or mixed with soil when used, which causes environmental risk and a reduction in herbicidal efficacy. In this study, the physicochemical properties were changed by using β-cyclodextrin (β-CD) to encapsulate diuron to form an inclusion complex. Some key technologies, including X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and nuclear magnetic resonance (1H NMR), were used to characterize the inclusion complex. The stoichiometry of the inclusion complex was determined by recording the 1H NMR spectrum or by using a diagram of inclusion ratios. A phase solubility study proved that the formed inclusion complex exhibited higher water solubility. Thermogravimetric analysis (TGA) demonstrated that the formed inclusion complex exhibited better thermal stability. Biological activity studies indicated that the herbicidal activity, in terms of herbicide removal, of the formed inclusion complex was higher than that of the original diuron. In general, the formation of the inclusion complex could reduce the environmental damage caused by diuron and enhance its herbicidal activity, providing an environmentally friendly method for using diuron.

scholarly journals CHARACTERIZATION AND INTRINSIC DISSOLUTION RATE STUDY OF MICROWAVE ASSISTED CYCLODEXTRIN INCLUSION COMPLEXES OF GEMFIBROZIL

2016 ◽  
Vol 8 (10) ◽  
pp. 160
Author(s):  
S. Ain ◽  
R. Singh ◽  
Q. Ain
Keyword(s):  
Inclusion Complex ◽  
Dissolution Rate ◽  
Inclusion Complexes ◽  
Microwave Drying ◽  
Phase Solubility ◽  
Intrinsic Dissolution ◽  
Intrinsic Dissolution Rate ◽  
Solubility Study ◽  
Microwave Assisted ◽  
Rate Study

<p><strong>Objective: </strong>The aim of the present study was to carry out characterization and intrinsic dissolution rate study of microwave assisted inclusion complex of poorly water soluble, lipid lowering agent gemfibrozil [5-(2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid]<strong> </strong>with naturally occurring β-cyclodextrins (CDs) or cycloheptaamylase.</p><p><strong>Methods: </strong>In this work, the phase solubility study was performed to find the ratio of drug and cyclodextrin complexes. Inclusion complexes were prepared by kneading and the prepared complex was subjected to microwave drying and conventional drying techniques. The prepared complexes were evaluated by intrinsic dissolution rate studies and equilibrium solubility study. Further characterization was done by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray powder diffractometry (DSC).</p><p><strong>Results: </strong>The phase solubility studies showed a linear A<sub>L</sub>-type diagram indicating the formation of inclusion complexes in 1:1 molar ratio β-CD-gemfibrozil complex with maximum stability constant of 148.88 M<sup>-1</sup>was selected for preparation of inclusion complex. The microwave dried product was identified as the inclusion complex with maximum IDR when compared to the conventional dried product.</p><p><strong>Conclusion: </strong>This study was concluded that the microwave drying is the most suitable of the previously occurring drying techniques. Since it showed the highest solubility and IDR value.</p>

scholarly journals Characterization, in Vitro and in Vivo Evaluation of Naringenin-Hydroxypropyl-β-Cyclodextrin Inclusion for Pulmonary Delivery

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 554 ◽  
Author(s):  
Minyi Guan ◽  
Rui Shi ◽  
Yuying Zheng ◽  
Xuan Zeng ◽  
Weiyang Fan ◽  
...  
Keyword(s):  
Pulmonary Delivery ◽  
Pharmacokinetic Profile ◽  
Proton Nuclear Magnetic Resonance ◽  
Flavonoid Compound ◽  
Phase Solubility ◽  
Local Concentration ◽  
Nmr Studies ◽  
Solubility Study ◽  
Phase Solubility Study

Naringenin, a flavonoid compound which exists abundantly in Citrus fruits, is proven to possess excellent antitussive and expectorant effects. However, the clinical applications of naringenin are restricted by its poor solubility and low local concentration by oral administration. The aim of the present study is to prepare a naringenin-hydroxypropyl-β-cyclodextrin (naringenin-HPβCD) inclusion as an inhalation solution for pulmonary delivery. The naringenin-HPβCD inclusion was characterized by phase solubility study, XRD, differential scanning calorimetry (DSC), proton nuclear magnetic resonance (1HNMR), and two-dimensional rotating frame Overhauser effect spectroscopy (2D ROESY). The in vitro permeability of the inclusion was evaluated on Calu-3 cells and the pharmacokinetic profile of pulmonary delivery was investigated in Sprague-Dawley (SD) rats. Based on the linear model of phase solubility study, the relationship between naringenin and HPβCD was identified as AL type with a 1:1 stoichiometry. XRD, DSC, and NMR studies indicated that the entire naringenin molecule is encapsulated into the cavity of HPβCD. HPβCD could increase the concentration of naringenin in the epithelium-lining fluid (ELF) of Calu-3 cells and act as a sustained release system for naringenin. The pharmacokinetic profile of naringenin-HPβCD inclusion showed rapid response and higher local concentration by pulmonary delivery. In conclusion, pulmonary delivery of naringenin-HPβCD inclusion is a promising formulation strategy, which could provide a new possibility for the clinical application of naringenin.

scholarly journals Inclusion Complex of Fexofenadine Hydrochloride with Cyclodextrins

2021 ◽  
Vol 11 (3) ◽  
pp. 282
Author(s):  
Melita Huremovic ◽  
Majda Srabovic ◽  
Mirsada Salihovic ◽  
Ekrem Pehlic
Keyword(s):  
Bathochromic Shift ◽  
Aqueous Solubility ◽  
Taste Masking ◽  
Solid Inclusion ◽  
Phase Solubility ◽  
Covalent Bonds ◽  
Molar Ratios ◽  
Solubility Study ◽  
Phase Solubility Study ◽  
Vis Spectroscopy

<p>Fexofenadine hydrochloride (FFN), (±)-4-[1-hydroxy-4[4-(hydroxydiphenylmethyl)-1-piperidinyl]-butyl] α,α-dimethylbenzeneacetic acid hydrochloride, is a second-generation antihistamine that is used to treat allergies. The drug is highly hydrophobic and slightly soluble in water. Cyclodextrins are widely used to improve the physicochemical and pharmaceutical properties such as solubility, stability, and bioavailability of poorly soluble drug molecules.Cyclodextrins can molecularly encapsulate various drugs into their hydrophobic cavity without forming any covalent bonds. Cyclodextrin (CDs), especially ß-Cyclodextrin (ß-CD), are widely used in the pharmaceutical field due to its ability to stabilize drug molecules and taste masking purposes.<strong> </strong></p><p>The phase solubility study was performed according to the method of Higuchi and Connors by adding the fexofenadine hydrochloride in excess to different concentrations of cyclodextrin solutions. Phase solubility study records show that the stability constant and complex stoichiometry of FFN-CD complexes increases linearly with CD concentration. Also, an increase in the concentration of β-cyclodextrin leads to an increase in the aqueous solubility of FFN. Complexes were analyzed by UV-VIS spectroscopy using the calibration curve of FFN. Also, UV-VIS spectra indicate a bathochromic shift which proves that complex formation has occurred.</p><p>Solid inclusion complexes of fexofenadine/β-cyclodextrin and its derivatives were prepared at the molar ratios of 1:1 by the physical mixing method. Characterization of the complexes was performed by using infrared spectroscopy. </p>

scholarly journals ENHANCEMENT OF SOLUBILITY AND BIOAVAILABILITY OF BCS CLASS-II AMBRISENTAN: IN VITRO, IN VIVO AND EX VIVO ANALYSIS

2022 ◽  
pp. 67-74
Author(s):  
RAHUL RADKE ◽  
NEETESH K. JAIN
Keyword(s):  
Solid Dispersion ◽  
Ex Vivo ◽  
Class Ii ◽  
Water Soluble ◽  
Pure Form ◽  
In Vitro Dissolution ◽  
Drug Solubility ◽  
Bcs Class Ii

Objective: The aim of this investigation was to enhance the solubility and bioavailability of the BCS class II poorly water-soluble drug ambrisentan by solid dispersion (SD) techniques using Gelucire 50/13 as a hydrophilic carrier. Methods: Solid dispersion of ambrisentan was prepared by kneading method using different dug: carrier ratios. Prepared SD was characterized for solubility, drug content, percentage yield, in vitro dissolution, ex vivo permeation and bioavailability. Solid-state characterization was performed by differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM). Results: All the SDs formulations showed increase in drug solubility and dissolution when compared with its pure form. Aqueous solubility of the drug was found to be increased 8.23 fold in SD. DSC study showed that endothermic peak of the drug was disappeared in spectra of SD, confirming its amorphous conversion, XRD study revealed the reduction to almost absence of specific high-intensity peaks of drug which confirmed the reduction of crysatallinity of ambrisentan in SD. SEM of optimized SD formulation demonstrates the complete encapsulation and solubilization drug. In vitro dissolution study showed that optimized SD formulation (ASD4) gives the faster drug release of 101.5% in 60 min, as compare to its pure form and other SD formulations. Conclusion: Solid dispersion ASD4 prepared with 1:4 drug to carrier ratio showed the highest drug solubility and in vitro dissolution. The ex vivo and in vivo studies performed on optimized formulation ASD4 showed enhancement in drug permeability and bioavailability in Gelucire 50/13 based SD formulation.

scholarly journals SOLID DISPERSION TECHNIQUE TO ENHANCE THE SOLUBILITY AND DISSOLUTION OF FEBUXOSTAT AN BCS CLASS II DRUG

2019 ◽  
Vol 11 (1) ◽  
pp. 241 ◽  
Author(s):  
D. Christopher Vimalson ◽  
S. Parimalakrishnan ◽  
N. S. Jeganathan ◽  
S. Anbazhagan
Keyword(s):  
Solid Dispersion ◽  
Solid Dispersions ◽  
Solvent Evaporation ◽  
Water Soluble ◽  
Fusion Method ◽  
Solvent Evaporation Method ◽  
Evaporation Method ◽  
Drug Content ◽  
Bcs Class Ii ◽  
Percentage Yield

Objective: The present study was aimed to enhance the solubility of poorly water-soluble drug (BCS Class II) Febuxostat using water-soluble polymers.Methods: Pre-formulation studies like drug excipient compatibility studies by Fourier-transform infrared spectroscopyDifferential scanning calorimetry and determination of saturation solubility of drug individually in various media like distilled water and pH 7.4 phosphate buffer. Solid dispersions of Febuxostat was prepared using Polyethylene glycol (PEG 6000) (fusion method) and Polyvinyl pyrrolidone (PVP K30) (solvent evaporation method) in various ratios like 1:1, 1:2, 1:3 and 1:4 separately. The formulated solid dispersions were evaluated for percentage yield, drug content and in vitro dissolution studies.Results: From the results of pre-formulation studies it was revealed that there was no interaction between drug and excipients and the pure drug was poorly soluble in water. The percentage yield of all formulations was in the range of 54-78 %, and drug content was in the range of 43-78 mg. The solid dispersion containing polyvinylpyrrolidone K 30 in 1:4 ratio showed the highest amount of drug release at the end of 30 min than other formulations.Conclusion: Finally it was concluded that solid dispersion prepared with PVP K-30 in 1:4 ratio by solvent evaporation method was more soluble than by fusion method.

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