scholarly journals Combined Self-Nanoemulsifying and Solid Dispersion Systems Showed Enhanced Cinnarizine Release in Hypochlorhydria/Achlorhydria Dissolution Model

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 627
Author(s):  
Ahmad A. Shahba ◽  
Ahmad Y. Tashish ◽  
Fars K. Alanazi ◽  
Mohsin Kazi
Keyword(s):  
Drug Release ◽  
Solid Dispersion ◽  
Negative Impact ◽  
Drug Dissolution ◽  
In Vitro Dissolution ◽  
Scanning Calorimetry ◽  
Dissolution Model ◽  
Dissolution Efficiency ◽  
Drug Free

The study aims to design a novel combination of drug-free solid self-nanoemulsifying drug delivery systems (S-SNEDDS) + solid dispersion (SD) to enhance cinnarizine (CN) dissolution at high pH environment caused by hypochlorhydria/achlorhydria. Drug-loaded and drug-free liquid SNEDDS were solidified using Neusilin® US2 at 1:1 and 1:2 ratios. Various CN-SDs were prepared using freeze drying and microwave technologies. The developed SDs were characterized by differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD). In-vitro dissolution studies were conducted to evaluate CN formulations at pH 6.8. Drug-free S-SNEDDSs showed acceptable self-emulsification and powder flow properties. DSC and XRD showed that CN was successfully amorphized into SDs. The combination of drug-free S-SNEDDS + pure CN showed negligible drug dissolution due to poor CN migration into the formed nanoemulsion droplets. CN-SDs and drug-loaded S-SNEDDS showed only 4% and 23% dissolution efficiency (DE) while (drug-free S-SNEDDS + FD-SD) combination showed 880% and 160% enhancement of total drug release compared to uncombined SD and drug-loaded S-SNEDDS, respectively. (Drug-free S-SNEDDS + SD) combination offer a potential approach to overcome the negative impact of hypochlorhydria/achlorhydria on drug absorption by enhancing dissolution at elevated pH environments. In addition, the systems minimize the adverse effect of adsorbent on drug release.

scholarly journals Amalgamation of Solid Dispersion and Melt Adsorption Techniques For Augmentation of Oral Bioavailability of Novel Anticoagulant Rivaroxaban

2021 ◽  
Author(s):  
Pranav Shah ◽  
Milan Patel ◽  
Jigar Shah ◽  
Anroop Nair ◽  
Sabna Kotta ◽  
...  
Keyword(s):  
Drug Release ◽  
Solid Dispersion ◽  
Oral Bioavailability ◽  
Drug Dissolution ◽  
Commercial Application ◽  
Scanning Calorimetry ◽  
Cytotoxicity Studies ◽  
Time Required ◽  
Saturated Solubility

Abstract The objective of the present study was to evaluate the potential of solid dispersion adsorbate to improve the solubility and bioavailability of rivaroxaban (RXN). Solid dispersion adsorbate (SDA) of RXN was developed by fusion method using PEG 4000 as carrier and Neusilin as adsorbent. A 32 full factorial design was utilized to formulate various SDAs. The selected independent variables were amount of carrier (X1) and amount of adsorbate (X2). The responses measured were time required for 85% drug release (Y1) and saturated solubility (Y2). MTT assay was employed for cytotoxicity studies on Caco-2 cells. In vivo pharmacokinetics and pharmacodynamic evaluations were carried out to assess the prepared SDA. Pre-compression evaluation of SDA suggests the prepared batches (B1-B9) possess adequate flow properties and could be used for compression of tablets. Differential scanning calorimetry and X-ray diffraction data signified the conversion of crystalline form of drug to amorphous form, a key parameter accountable for improvement in drug dissolution. Optimization data suggests that the amount of carrier and amount of adsorbate significantly (P < 0.05) influence both dependent variables (time required for 85% drug release and saturated solubility). Post-compression data signifies that the compressibility behavior of prepared tablets were within the official standard limits. Significant increase (P < 0.0001) in the in vitro dissolution characteristics of RXN was noticed in optimized SDA (>85% in 10 min) as compared to pure drug, marketed product and directly compressible tablet. Cytotoxicity studies confirm nontoxicity of prepared RXN SDA tablets. Higher Cmax and AUC achieved with RXN SDA tablets indicated enhancement in oral bioavailability (~3 folds higher than the RXN suspension). Higher bleeding time and percentage of platelet aggregation noticed with RXN SDA tablets further substantiate the efficacy of the prepared formulation. In summary, the results showed the potential of RXN SDA tablets to enhance the bioavailability of RXN and hence can be an alternate approach of solid dosage form for its development for commercial application.

scholarly journals DESIGN, OPTIMIZATION, AND EVALUATION OF ACYCLOVIR FAST DISSOLVING TABLETS EMPLOYING STACH PHTHALATE – A NOVEL SUPERDISINTEGRANT

2019 ◽  
pp. 132-142 ◽  
Author(s):  
SANTOSH KUMAR R ◽  
ANNU KUMARI
Keyword(s):  
Drug Dissolution ◽  
In Vitro Dissolution ◽  
Scanning Calorimetry ◽  
Disintegration Time ◽  
Drug Content ◽  
Enhanced Dissolution ◽  
Wetting Time ◽  
Croscarmellose Sodium ◽  
Dissolution Efficiency

Objective: The objective of the present research was to prepare starch phthalate (a novel superdisintegrant) and to optimize and formulate acyclovir fast dissolving tablets employing 23 factorial design using starch phthalate as superdisintegrant. Materials and Methods: Drug excipient compatibility studies such as Fourier-transform infrared spectroscopy, differential scanning calorimetry, and thin-layer chromatography were carried out to check the drug interaction between acyclovir and starch phthalate. The direct compression method was used for tablet preparation. Prepared tablets were then evaluated for hardness, friability, drug content, disintegration time, water absorption, and wetting time, in vitro dissolution studies. Response surface plots and contour plots were also plotted to know the main effects and interaction effects of independent variables (starch phthalate [A], croscarmellose sodium [B], and crospovidone [C] on dependent variables [disintegration time and drug dissolution efficiency in 1 min]) and stability studies were also done. Results: Tablets of all formulations were of good quality concerning drug content (100±5%), hardness (3.6–4.0 kg/cm2), and friability (<0.16%). In all formulations, formulation F8 found to be optimized formulation with least disintegration time 9±3 s, less wetting time 10±0.17 s, and enhanced dissolution rate in 1 min, i.e., 99.92±0.11 as compared to other formulation. Conclusion: From the research, it was concluded that on combination with crospovidone (5%) and croscarmellose sodium (5%), starch phthalate (10%) enhanced the dissolution efficiency of the drug. Hence, starch phthalate can be used as a novel disintegrant in the manufacturing of fast dissolving tablets.

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.

scholarly journals Enrichment of aqueous solubility and dissolution profile of mesalamine: In vitro evaluation of solid dispersion

2021 ◽  
Vol 9 (2) ◽  
pp. 127-135
Author(s):  
Anil Raosaheb Pawar ◽  
Pralhad Vitthalrao Mundhe ◽  
Vinayak Kashinath Deshmukh ◽  
Ramdas Bhanudas Pandhare ◽  
Tanaji Dilip Nandgude
Keyword(s):  
Ulcerative Colitis ◽  
Drug Release ◽  
Dissolution Rate ◽  
Solid Dispersion ◽  
Solid Dispersions ◽  
Aqueous Solubility ◽  
In Vitro Dissolution ◽  
Dissolution Profile ◽  
Peg 4000

The aim of the present study was to formulate solid dispersion (SD) of Mesalamine to enrich the aqueous solubility and dissolution rate. Mesalamine is used in the management of acute ulcerative colitis and for the prevention of relapse of active ulcerative colitis. In the present study, Solid dispersion of Mesalamine was prepared by Fusion and Solvent evaporation method with different polymers. SD’s were characterized by % practical yield, drug content, Solubility, FT-IR, PXRD (Powder X- ray diffractometry), SEM (Scanning electron microscopy), in vitro dissolution studies and Stability studies. The percent drug release of prepared solid dispersion of Mesalamine by fusion and solid dispersion method (FM47, FM67, SE47 and SE67) in 1:7 ratio was found 81.36±0.41, 86.29±0.64, 82.45±0.57and 87.25±1.14 respectively. The aqueous solubility and percent drug release of solid dispersion of Mesalamine by both methods was significantly increased. The PXRD demonstrated that there was a significant decrease in crystallinity of pure drug present in the solid dispersions, which resulted in an increased aqueous solubility and dissolution rate of Mesalamine.The significant increase in aqueous solubility and dissolution rate of Mesalamine was observed in solid dispersion as the crystallinity of the drug decreased, absence of aggregation and agglomeration, increased wetability and good dispersibility after addition of PEG 4000 and PEG 6000.

scholarly journals Crushed Tablets: Does the Administration of Food Vehicles and Thickened Fluids to Aid Medication Swallowing Alter Drug Release?

2014 ◽  
Vol 17 (2) ◽  
pp. 207 ◽  
Author(s):  
Yady Juliana Manrique-Torres ◽  
Danielle J Lee ◽  
Faiza Islam ◽  
Lisa M Nissen ◽  
Julie A.Y. Cichero ◽  
...  
Keyword(s):  
Drug Release ◽  
Orange Juice ◽  
Immediate Release ◽  
Drug Dissolution ◽  
In Vitro Dissolution ◽  
Simulated Gastric Fluid ◽  
Drug Bioavailability ◽  
Thickening Agents

Purpose. To evaluate the influence of co-administered vehicles on in vitro dissolution in simulated gastric fluid of crushed immediate release tablets as an indicator for potential drug bioavailability compromise. Methods. Release and dissolution of crushed amlodipine, atenolol, carbamazepine and warfarin tablets were tested with six foods and drinks that are frequently used in the clinical setting as mixers for crushed medications (water, orange juice, honey, yoghurt, strawberry jam and water thickened with Easythick powder) in comparison to whole tablets. Five commercial thickening agents (Easythick Advanced, Janbak F, Karicare, Nutilis, Viscaid) at three thickness levels were tested for their effect on the dissolution of crushed atenolol tablets. Results. Atenolol dissolution was unaffected by mixing crushed tablets with thin fluids or food mixers in comparison to whole tablets or crushed tablets in water, but amlodipine was delayed by mixing with jam. Mixing crushed warfarin and carbamazepine tablets with honey, jam or yoghurt caused them to resemble the slow dissolution of whole tablets rather than the faster dissolution of crushed tablets in water or orange juice. Crushing and mixing any of the four medications with thickened water caused a significant delay in dissolution. When tested with atenolol, all types of thickening agents at the greatest thickness significantly restricted dissolution, and products that are primarily based on xanthan gum also delayed dissolution at the intermediate thickness level. Conclusions. Dissolution testing, while simplistic, is a widely used and accepted method for comparing drug release from different formulations as an indicator for in vivo bioavailability. Thickened fluids have the potential to retard drug dissolution when used at the thickest levels. These findings highlight potential clinical implications of the addition of these agents to medications for the purpose of dose delivery and indicate that further investigation of thickened fluids and their potential to influence therapeutic outcomes is warranted. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Non-compendial vs compendial analytical tests - a powerful tool for predicting in vitro similarity of highly viscous oral suspension

2019 ◽  
Vol 64 (02) ◽  
pp. 61-72
Author(s):  
Elena Kazandjievska ◽  
Iva Antova ◽  
Slavica Mitrevska ◽  
Aleksandar Dimkovski ◽  
Elena Dimov ◽  
...  
Keyword(s):  
Drug Release ◽  
Negative Impact ◽  
In Vitro Release ◽  
Active Pharmaceutical Ingredient ◽  
Pharmaceutical Products ◽  
Dosage Forms ◽  
Oral Suspension ◽  
In Vitro Dissolution ◽  
Dissolution Profile

In vitro dissolution profiles are increasingly used to evaluate drug release characteristics of pharmaceutical products. The dissolution methods is expected to be an appropriate tool for checking consistency of the pharmaceutical attributes by discriminating similarities and dissimilarities between different drug formulations. Expansion in development of novel “special” dosage forms, due to the manner in which these dosage forms release the active pharmaceutical ingredient, usually requires applying non-compendial dissolution strategy that differs from the traditional compendial recommendations. For demonstrating sameness in the dissolution profile, in vitro drug release comparison between test and reference product of highly viscous oral suspension by applying non-compendial peak vessel against conventional hemispheric vessel was demonstrated in this study. All reference batches exhibited high variability in dissolution data when using hemispheric vessel due to forming mound compact mass at the bottom of the vessel. Different strategies for samples manipulation, before and during dissolution period, were performed in order to eliminate additional variabilities. Modifications of conventional USP 2 apparatus such as using peak vessel provided with more reproducible and reliable result for distinguishing in vitro similarities between different formulations of oral suspensions. Misinterpretation of dissolution data can lead to negative impact on product development. Taking time to observe and evaluate what is happening to the product in the vessel during dissolution is of curtail consideration for proper selection of the dissolution strategy. Keywords: oral suspensions; in-vitro release; hydrodynamic variability; USP apparatus 2/ Paddle apparatus; peak vessel

scholarly journals Formulation of Ramipril Tablets Containing Solid Dispersion Employing Selective Polymers to Enhance Dissolution Rate

2020 ◽  
Vol 10 (3-s) ◽  
pp. 142-149
Author(s):  
Inder Kumar ◽  
Sandeep Verma ◽  
Amit Chaudhary
Keyword(s):  
Drug Release ◽  
Dissolution Rate ◽  
Solid Dispersion ◽  
Phosphate Buffer ◽  
Flow Property ◽  
In Vitro Dissolution ◽  
Standard Data ◽  
Evaporation Technique ◽  
Good Flow

Objective: The present work based on formulation of Ramipril tablets containing solid dispersion employing selective polymers. The objective of the preparation is to prepare the solid dispersion of the Ramipril, which has more responsive value in terms of the dissolution rate. Method: Solid dispersion complex was prepared with two different carriers PEG 6000 and PVP K30. Nine formulations were developed and each formulation were subjected to pre compression and post compression parameters. Result and Discussion:  Pre-compression and post compression parameters were studied which had shown good flow property and compiled the standard data. In-vitro dissolution studies shows more than 90 % drug release in phosphate buffer pH 6.8 in 30 min. Out of all formulation F4 showed 92.55±0.67 % drug release with in 30min which was the best result rest of the formulation. Conclusion: Ramipril tablets were successfully prepared and evaluated. F4 formulation shows the greater dissolution rate in phosphate buffer pH 6.8 as compared to other formulations. When compared with marketed formulation it also shows better results. Therefore, Ramipril solid dispersion tablets enhanced the dissolution rate and can be more efficacious for improving oral bioavailability of Ramipril. Keywords: Solid dispersion, Ramipril, Solvent Evaporation Technique.

scholarly journals FORMULATION AND OPTIMIZATION OF CURCUMIN SOLID DISPERSION PELLETS FOR IMPROVED SOLUBILITY

2019 ◽  
pp. 36-46
Author(s):  
SANJEEVANI DESHKAR ◽  
ARUN SATPUTE
Keyword(s):  
Solid Dispersion ◽  
Weight Ratio ◽  
Poloxamer 407 ◽  
Drug Dissolution ◽  
In Vitro Dissolution ◽  
Phase Solubility ◽  
Dsc Studies ◽  
Poorly Soluble ◽  
Extrusion Spheronization

Objective: The present study was aimed at designing of solid dispersion based pellets of curcumin (Cu) for improving its solubility. Methods: Solid dispersion (SD) of Cu was prepared by the melt method using Poloxamer 407 (Pol 407) at a different weight ratio of Cu-Pol 407 (1:2, 1:3, 1:5, 1:7, 1:10). The solid dispersion was characterised by FTIR, SEM, DSC, XRD and evaluated for saturation solubility in water, drug content and in vitro dissolution. The pellets of Cu solid dispersion were prepared by extrusion spheronization technique and optimization was performed by 32full factorial design. The pellets were evaluated for size distribution, flow properties, hardness, disintegration and in vitro drug dissolution. Results: From the phase solubility analysis, Pol 407 was selected as a Solid dispersion carrier. The formation of Cu-SD by melt method using Pol 407, was confirmed from FTIR and DSC studies. XRD studies indicated a change of Cu from crystalline to amorphous form. There was a significant increase of Cu when formulated as SD compared to plain Cu. The optimization of extrusion spheronization process revealed the significant effect of Cu-Pol 407 ratio (p<0.0001) on in vitro dissolution of pellets. Higher Cu dissolution was obtained with Cu-SD pellets compared to plain Cu pellets. Conclusion: The present study demonstrated the potential of Cu-SD pellets in improving the solubility of poorly soluble Cu.

scholarly journals OPTIMIZATION OF STATISTICALLY DESIGNED ACECLOFENAC FAST DISSOLVING TABLETS EMPLOYING STARCH GLUTAMATE AS A NOVEL SUPERDISINTEGRANT

2019 ◽  
pp. 77-88
Author(s):  
R. SANTOSH KUMAR ◽  
SAHITHI MUDILI
Keyword(s):  
Drug Release ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
In Vitro Dissolution ◽  
Pharmacokinetic Studies ◽  
Disintegration Time ◽  
Short Period ◽  
Dissolution Efficiency

Objective: To optimize aceclofenac fast dissolving tablets employing starch glutamate as novel superdisintegrant by 23factorial design to improve bioavailability and enhance patient compliance. Methods: Starch glutamate was prepared by the esterification process. Starch glutamate physical and micromeritics properties had been evaluated and the prepared starch glutamate was used as a superdisintegrant for the formulation of the fast dissolving tablets of aceclofenac by direct compression method and optimized by employing 23factorial design. The prepared aceclofenac fast dissolving tablets were evaluated for post compression parameters as well as in vitro and in vivo release characteristics. Optimized formulation stability studies were performed at accelerated conditions for 6 mo as per ICH and WHO guidelines. Results: The prepared starch glutamate was amorphous, insoluble in aqueous and organic solvents were tested. Fast dissolving tablets of aceclofenac were formulated by employing starch glutamate as a superdisintegrant showed good tablet properties and showed an increased dissolution efficiency of the drug. Among all the formulations (F1 to F8), the formulation F8 containing 5% concentration of starch glutamate, croscarmellose sodium and, crospovidone as a superdisintegrants showed 99.7±0.15% of drug release within 5 min. Whereas the formulation F2 containing 5% concentration of starch glutamate, drug release characters were comparable to the formulation F8. Optimized formulation F2 attained peak plasma concentration within a short period and showed increased relative bioavailability of the drug. Conclusion: From the physical properties, disintegration time, in vitro dissolution studies and pharmacokinetic studies, it was concluded that fast dissolving tablets of aceclofenac tablets formulated by employing starch glutamate as a superdisintegrant enhanced the dissolution efficiency and improved the bioavailability of the drug as compared to the pure drug and stable.

Formulation and In Vivo Evaluation of Mucoadhesive Buccal Tablets of Carvedilol

2013 ◽  
Vol 6 (3) ◽  
pp. 2164-2171
Author(s):  
S. B. Shirsand ◽  
G V Wadageri ◽  
S A Raju ◽  
Gopikrishna Kolli
Keyword(s):  
Drug Release ◽  
Residence Time ◽  
Hydroxypropyl Methylcellulose ◽  
Drug Dissolution ◽  
In Vitro Dissolution ◽  
Stability Studies ◽  
Matrix Layer ◽  
Buccal Tablets ◽  
Carbopol 934P

In present study we studied the feasibility of preparing mucoadhesive buccal delivery systems containing carvedilol to improve drug residence time on buccal mucosa and drug dissolution rate, to circumvent the first-pass metabolism and quick drug entry into the systemic circulation. Bilayer buccal tablets of carvedilol prepared using controlled release and mucoadhesive polymers (hydroxypropyl methylcellulose 15 cps, 50 cps, K4M and Carbopol 934p) along with impermeable backing layer (ethyl cellulose). 15 formulations were developed with varying concentrations of polymers. The designed tablets were evaluated for tablet size, shape, in vitro drug release, stability studies, bioavailability studies and drug-excipients interaction (FTIR). Among the 15 formulations, F151 containing hydroxypropyl methylcellulose 15 cps (48% w/w of matrix layer), Carbopol 934p (2% w/w of matrix layer) and mannitol (channeling agent, 34.5% w/w of matrix layer) was found to be promising. Dissolution tests revealed that 84.73% of carvedilol was dissolved from the formulation F151 in 8 h along with satisfactory bio adhesion strength (5.71 g). Bioavailability studies of the promising formulation were compared with that of the oral solution.  The percentage relative bioavailability of the buccal tablets was found to be 121.27%. Stability studies, on the promising formulation indicated that there are no significant changes in drug content and in vitro dissolution characteristics (p<0.05). FTIR studies show no evidence of interaction between drug and excipients. It was concluded that mucoadhesive buccal tablets of carvedilol with controlled unidirectional drug release along with satisfactory bioadhesion strength and with sufficient residence time can be successfully developed by direct compression method.

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