scholarly journals Different BCS Class II Drug-Gelucire Solid Dispersions Prepared by Spray Congealing: Evaluation of Solid State Properties and In Vitro Performances

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 548 ◽  
Author(s):  
Serena Bertoni ◽  
Beatrice Albertini ◽  
Nadia Passerini
Keyword(s):  
Solid State ◽  
Drug Carrier ◽  
Solid Dispersions ◽  
Class Ii ◽  
Water Soluble ◽  
Drug Dissolution ◽  
Crystalline Solid ◽  
Dissolution Behavior ◽  
Bcs Class Ii

Delivery of poorly water soluble active pharmaceutical ingredients (APIs) by semi-crystalline solid dispersions prepared by spray congealing in form of microparticles (MPs) is an emerging method to increase their oral bioavailability. In this study, solid dispersions based on hydrophilic Gelucires® (Gelucire® 50/13 and Gelucire® 48/16 in different ratio) of three BCS class II model compounds (carbamazepine, CBZ, tolbutamide, TBM, and cinnarizine, CIN) having different physicochemical properties (logP, pKa, Tm) were produced by spray congealing process. The obtained MPs were investigated in terms of morphology, particles size, drug content, solid state properties, drug-carrier interactions, solubility, and dissolution performances. The solid-state characterization showed that the properties of the incorporated drug had a profound influence on the structure of the obtained solid dispersion: CBZ recrystallized in a different polymorphic form, TBM crystallinity was significantly reduced as a result of specific interactions with the carrier, while smaller crystals were observed in case of CIN. The in vitro tests suggested that the drug solubility was mainly influenced by carrier composition, while the drug dissolution behavior was affected by the API solid state in the MPs after the spray congealing process. Among the tested APIs, TBM-Gelucire dispersions showed the highest enhancement in drug dissolution as a result of the reduced drug crystallinity.

scholarly journals DEVELOPMENT AND IN VITRO DISSOLUTION STUDY OF BINARY AND TERNARY SOLID DISPERSIONS OF ACECLOFENAC

2019 ◽  
Author(s):  
Md. Shahidul Islam ◽  
Rasheda Akter Lucky
Keyword(s):  
Polyethylene Glycol ◽  
Dissolution Rate ◽  
Solid Dispersion ◽  
Drug Carrier ◽  
Solid Dispersions ◽  
Weight Ratio ◽  
Water Soluble ◽  
In Vitro Dissolution ◽  
Peg 6000

The poor aqueous solubility of the drug exhibits in variable dissolution rate and hence poor bioavailability. Aceclofenac is poorly water soluble drug. The aim of the present study was to improve the water solubility and the dissolution rate of Aceclofenac by solid dispersion technique using different water soluble polymers. The term solid dispersions refer to the dispersions of one or more active ingredients in an inert carrier or matrix at solid state. In this study, binary solid dispersion of Aceclofenac were prepared by fusion method using Polyethylene glycol 6000 (PEG 6000), Polyethylene glycol 4000 (PEG 4000), Poloxamer as carrier. Different drug-carrier weight ratio was used for this study. The effect of the carrier on the solubility and in-vitro dissolution were studied. It was found the drug was released 26.86% after 5 minutes and only 40.19% within 60 mins from active Aceclofenac on the other hand the release pattern of Aceclofenac from the binary SD formulation containing PEG 6000 in 1:5 ratio (Formulation coding: A5) showed the best result in comparison of other binary and ternary SD formulations which was 62.29% after 5 min and 83.03% within 60 mins. The hydrophilic polymers used for the preparation of solid dispersion are showed significant increase in the solubility of Aceclofenac.

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 Formulation Development and Evaluation of Liposphere of Poor Water Soluble Drug for Hyperlipidemia

2021 ◽  
Vol 11 (2) ◽  
pp. 23-30
Author(s):  
Anil Kumar ◽  
Umesh K. Jain ◽  
Ajay Patel
Keyword(s):  
Drug Release ◽  
Stearic Acid ◽  
Aqueous Solubility ◽  
Class Ii ◽  
Water Soluble ◽  
Fibric Acid Derivative ◽  
Formulation Development ◽  
Bcs Class Ii ◽  
Paraffin Oil

Lipospheres offer a new approach to improve an aqueous solubility of BCS class-II drugs. Simvastatin is a third generation fibric acid derivative belonging to this class, employed clinically as a hypolipidemic agent to lessen the risk caused by atherosclerosis. An attempt was made to improve aqueous solubility of Simvastatin by aid of stearic acid and Paraffin oil. The factorial batches of the Simvastatin lipospheres were formulated by melt dispersion technique using 32 factorial design with variables X1- concentration of stearic acid and X2- concentration of paraffin oil and responses Y1 - % Drug Entrapment (% DE) and Y2 - % Drug Release (% DR). From the surface response graphs the optimized batch was formulated and evaluated for saturation solubility, in-vitro drug release studies. Significant improvement in the aqueous solubility of the drug in the Simvastatin lipospheres supports the applicability of lipospheres as a tool for improving aqueous solubility of the BCS class-II drugs. Keywords: Linospheres; Simvastatin; Drug release; Hyperlipidemic; Drug entrapment.

Improved Efficacy of Lovastatin from Soluplus-PEG Hybrid Polymer- Based Binary Dispersions

2020 ◽  
Vol 16 (8) ◽  
pp. 1164-1171
Author(s):  
Radhika Verma ◽  
Manju Nagpal ◽  
Thakur G. Singh ◽  
Manjinder Singh ◽  
Geeta Aggarwal
Keyword(s):  
Drug Release ◽  
Solid Dispersions ◽  
Class Ii ◽  
Hybrid Polymer ◽  
In Vitro Drug Release ◽  
In Vivo Efficacy ◽  
Bcs Class Ii ◽  
Individual Polymer

Background: Lovastatin is a statin drug used for lowering cholesterol in those with hypercholesterolemia to reduce the risk of cardiovascular disease. It is a BCS class II drug i.e. it has low aqueous solubility and high permeability. Objective: Improvement of solubility and in vivo efficacy was investigated by formulating binary solid dispersions. Methods: Binary solid dispersions of lovastatin were formulated in the current study using two polymers i.e. Soluplus and PEG 4000. Seven batches of solid dispersions were prepared (S1, P1, SP1, SP2, SP3, SP4, and SP5) via the solvent evaporation method. The prepared dispersions were evaluated for equilibrium solubility, FTIR, XRD, DSC, SEM studies, and further in vitro drug release were evaluated. The results revealed significant enhancement in the solubility of drug-using polymer hybrids as compared to that of individual polymer dispersion batches. Results: A significant solubility enhancement was observed with SP5 (approx 40 times) having a higher concentration of Soluplus. FTIR studies indicated no drug to polymer interaction. DSC studies revealed complete amorphization of polymer and also X-RD data is also in compliance with DSC results. In vitro drug release studies showed almost 100% release in 2h in polymer hybrid batches in comparison to individual polymer batch (S1 and P1). The best dissolution characteristics were observed in SP3 and SP5 which is also in compliance with solubility data. Further in vivo efficacy studies revealed a significant reduction in LDL, HDL, TG, AST, and ALT levels in comparison to pure drug lovastatin group and hypercholesterolemia control group. Conclusion: Hybrid polymer may be a prospective carrier system for the enhancement of solubility of BCS class II drugs.

scholarly journals Physicochemical characterization and in vitro dissolution behavior of olanzapine-mannitol solid dispersions

2012 ◽  
Vol 48 (2) ◽  
pp. 243-255 ◽  
Author(s):  
Venkateskumar Krishnamoorthy ◽  
Suchandrasen ◽  
Verma Priya Ranjan Prasad
Keyword(s):  
Solid State ◽  
Solid Dispersions ◽  
In Vitro Dissolution ◽  
Dissolution Behavior ◽  
Phase Solubility ◽  
Permeation Studies ◽  
Ft Ir ◽  
Solubility Studies ◽  
Solid State Characterization

The objective of the present work is to study the dissolution behavior of olanzapine from its solid dispersions with mannitol. Solid dispersions were prepared by melt dispersion method and characterized by phase solubility studies, drug content and in vitro dissolution studies. The best releasing dispersions were selected from release data, dissolution parameters and their release profiles. Solid state characterization techniques like Fourier transform infrared (FT-IR) spectroscopy, X-ray diffractometry, differential scanning calorimetry, near-infrared and Raman spectroscopy were used to characterize the drug in selected dispersions. The dispersions were also evaluated by wettability studies and permeation studies. The results of phase solubility studies and the thermodynamic parameters indicated the spontaneity and solubilization effect of the carrier. The release study results showed greater improvement of drug release from solid dispersions compared to pure drug, and the release was found to increase with an increase in carrier content. The possible mechanism for increased release rate from dispersions may be attributed to solubilization effect of the carrier, change in crystal quality, phase transition from crystalline to amorphous state, prevention of agglomeration or aggregation of drug particles, change in surface hydrophobicity of the drug, and increased wettability and dispersability of the drug in dissolution medium. The suggested reasons for increased release rate from dispersions were found to be well supported by results of solid state characterization, wettability and permeation studies. The absence of any interaction between the drug and the carrier was also proved by FT-IR analysis.

scholarly journals Formulation, Development, Evaluation and Solubility Enhancement of Lercanidipine Hydrochloride by Solid Dispersion Techniques

2021 ◽  
pp. 195-213
Author(s):  
S. D. Mankar ◽  
Punit R. Rachh
Keyword(s):  
Solid State ◽  
Solid Dispersion ◽  
Drug Carrier ◽  
Solid Dispersions ◽  
Water Soluble ◽  
Formulation Development ◽  
Scanning Calorimetry ◽  
Onset Of Action ◽  
Drug Molecules ◽  
Lercanidipine Hydrochloride

Background: Solid dispersions (SDs) are the dispersion of hydrophobic drugs in an inert hydrophilic carrier. SDs are prepared to improve the dissolution properties and bioavailability of slightly water-soluble drug molecules by dispersing them into an inert hydrophilic carrier. Aims and Objective: Evaluate the dissolution and solubility of Solid Dispersion of Lercanidipine Hydrochloride (LER). Materials and Methods: To study the effect of polymer, dissolution and solubility studies were carried out. Solid state characterizations of prepared solid dispersions were performed by differential scanning calorimetry (DSC).Drug- carrier interactions were studied by FT-IR spectroscopy, whereas X-ray diffraction of powder was done to demonstrate the crystal structure of the dispersions. Results: The prepared solid dispersion exhibited 94% drug release at 30 minutes which is higher than both LER pure and LER MKT. Better dissolution characteristic of solid dispersion was confirmed by 9.86 min MDT and 63.12% DE30 which is higher than that of LER MKT (13.64 MDT, 46.92 % DE30) Solid state characterization revealed that enhancement of dissolution is the result of conversion of crystalline form of LER to less crystalline and/or amorphous form. Conclusion: Solid dispersion of LER can successfully be prepared with the PEG6000 in the ratio of 1:6 using solvent evaporation technique. It is a successful and easy approach for the increase in onset of action of drug after administration and facilitates treatment of cardiovascular diseases.

scholarly journals DEVELOPMENT AND IN VITRO EVALUATION OF SOLID DISPERSIONS OF CANDESARTAN CILEXETIL

2019 ◽  
pp. 233-241
Author(s):  
Bhikshapathi D.v.r.n.
Keyword(s):  
Candesartan Cilexetil ◽  
Drug Carrier ◽  
Solid Dispersions ◽  
Solvent Evaporation ◽  
Water Soluble ◽  
In Vitro Dissolution ◽  
Optimized Design ◽  
Water Soluble Drugs ◽  
Effective Group

Objective The main objective of the present study is systematic development of solid dispersions of Candesartan cilexetil by solvent evaporation method to enhance the solubility and bioavailability. Methods In the present study, eighteen formulations of solid dispersions were prepared with 1:1 and 1:3 ratios of drug: carrier and with and without surfactant. There was significant improvement in the rate of drug release from all 20 solid dispersions and the formulation (SD16) comprising Candesartan: containing Soluplus (1:3 ratio of drug:  Soluplus with 2% SLS as surfactant) by solvent evaporation process. Results Final optimized design SD16 contained maximum drug content of 99.08%. In in vitro dissolution studies it shows greater dissolution rate i.e. 99.7±4.2% associated through additional designs and pure drug. The drug was compatible with all the excipients as per FTIR (Fourier transform infrared spectroscopy). From powder X-ray diffraction (p-XRD) and by (SEM) studies it was evident that crystalline form of Candesartan has been converted into amorphous form within solid dispersion design.  Conclusion From these studies we can accomplish solid dispersions are one of the greatest favorable formulation for Candesartan cilexetil for enhancing the solubility and bioavailability of poorly water soluble drugs in the effective group of hypertension and other cardiac problems.

Solid State Analysis and In-Vitro Dissolution Behavior of MeloxicamHydroxy Propyl Beta Cyclodextrin-Ethanolamines Ternary Complexes

2018 ◽  
Vol 9 (01) ◽  
Author(s):  
Jafar M. ◽  
Salahuddin M. ◽  
Kayed T. S. ◽  
Ahmad N M. ◽  
Al-Eid H. A. ◽  
...  
Keyword(s):  
Solid State ◽  
Ternary Complex ◽  
Solvent Evaporation ◽  
Ternary Complexes ◽  
Drug Dissolution ◽  
Dissolution Behavior ◽  
Binary Complex ◽  
Binary Complexes ◽  
State Analysis

The present study was aimed to improve the aqueous solubility and dissolution rate of an NSAID meloxicam by hydroxy propyl β-cyclodextrin ternary complexes employing ethanolamines. Initially, meloxicam (MLX) binary complexes with Hydroxy propyl β-Cyclodextrin (HPβCD) were formulated by kneading and solvent evaporation techniques which was followed by ternary complex preparation of selected MLX-HPβCD binary complex employing different ethanolamines by solvent evaporation method. The solvent evaporationwas used in preparing ternary complexes of MLX, because it was proved to be the best method comparatively in yielding promising binary complexes of meloxicam in the initial stage of this study. MLX formed 1:1 M stoichiometric binary and ternary inclusion complexes as demonstrated by the AL-type of phase solubility curve. An increment in the stability constant value (Kc) of MLX- HPβCD complex in the presence of ethanolamines conceded higher complexation efficiency. Solid state analysis (FTIR, TGA, and SEM studies) of ternary compounds evidenced the perfect inclusion complex formation. Ternary complexes showed significant improvement in drug dissolution compared topure MLX and MLX-HPβCD binary complex. The ternary complex containing 1:1:1 molar ratio of MLX-HPβCD-DEA exhibited 86.91% drug dissolution in 1 hour, which was significantly high in relation to ternary complexes containing mono and tri ethanolamines, and it was found to follow imperatively matrix order release mechanism. On aging studied complexes showed no significant change in physical appearance, drug content and drug dissolution attributes, which clearly shows high in-vitro stability of the complexes.

Fenofibrate Solid Dispersion for Improving Oral Bioavailability: Preparation, and Characterization and in vivo Evaluation

2020 ◽  
Vol 13 (5) ◽  
pp. 5102-5109
Author(s):  
Venu Madhav K ◽  
Somnath De ◽  
Chandra Shekar Bonagiri ◽  
Sridhar Babu Gummadi
Keyword(s):  
Oral Bioavailability ◽  
Oral Delivery ◽  
Solid Dispersions ◽  
In Vitro Release ◽  
Aqueous Solubility ◽  
Water Soluble ◽  
Scanning Calorimetry ◽  
In Vivo Evaluation

Fenofibrate (FN) is used in the treatment of hypercholesterolemia. It shows poor dissolution and poor oral bioavailability after oral administration due to high liphophilicity and low aqueous solubility. Hence, solid dispersions (SDs) of FN (FN-SDs) were develop that might enhance the dissolution and subsequently oral bioavailability. FN-SDs were prepared by solvent casting method using different carriers (PEG 4000, PEG 6000, β cyclodextrin and HP β cyclodextrin) in different proportions (0.25%, 0.5%, 0.75% and 1% w/v). FN-SDs were evaluated solubility, assay and in vitro release studies for the optimization of SD formulation. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM) analysis was performed for crystalline and morphology analysis, respectively. Further, optimized FN-SD formulation evaluated for pharmacokinetic performance in Wistar rats, in vivo in comparison with FN suspension.  From the results, FN-SD3 and FN-SD6 have showed 102.9 ±1.3% and 105.5±3.1% drug release, respectively in 2 h. DSC and PXRD studies revealed that conversion of crystalline to amorphous nature of FN from FT-SD formulation. SEM studies revealed the change in the orientation of FN when incorporated in SDs. The oral bioavailability FN-SD3 and FN-SD6 formulations exhibited 2.5-folds and 3.1-folds improvement when compared to FN suspension as control. Overall, SD of FN could be considered as an alternative dosage form for the enhancement of oral delivery of poorly water-soluble FN.

Amorphous and Crystalline Particulates: Challenges and Perspectives in Drug Delivery

2017 ◽  
Vol 23 (3) ◽  
pp. 350-361 ◽  
Author(s):  
Hisham Al-Obaidi ◽  
Mridul Majumder ◽  
Fiza Bari
Keyword(s):  
Crystal Engineering ◽  
Drug Carrier ◽  
Solid Dispersions ◽  
Chemical Properties ◽  
Pharmaceutical Product ◽  
Water Soluble ◽  
Amorphous Form ◽  
Physico Chemical ◽  
Water Soluble Drugs ◽  
Amorphous Drug

Crystalline and amorphous dispersions have been the focus of academic and industrial research due to their potential role in formulating poorly water-soluble drugs. This review looks at the progress made starting with crystalline carriers in the form of eutectics moving towards more complex crystalline mixtures. It also covers using glassy polymers to maintain the drug as amorphous exhibiting higher energy and entropy. However, the amorphous form tends to recrystallize on storage, which limits the benefits of this approach. Specific interactions between the drug and the polymer may retard this spontaneous conversion of the amorphous drug. Some studies have shown that it is possible to maintain the drug in the amorphous form for extended periods of time. For the drug and the polymer to form a stable mixture they have to be miscible on a molecular basis. Another form of solid dispersions is pharmaceutical co-crystals, for which research has focused on understanding the chemistry, crystal engineering and physico-chemical properties. USFDA has issued a guidance in April 2013 suggesting that the co-crystals as a pharmaceutical product may be a reality; but just not yet! While some of the research is still oriented towards application of these carriers, understanding the mechanism by which drug-carrier miscibility occurs is also covered. Within this context is the use of thermodynamic models such as Flory-Huggins model with some examples of studies used to predict miscibility.

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