Co-amorphous palbociclib–organic acid systems with increased dissolution rate, enhanced physical stability and equivalent biosafety

The content of this investigation was to study the influence of β-cyclodextrin and hydroxy propyl-β-cyclodextrin complexation on enhancement of solubility and dissolution rate of isradipine. Based on preliminary phase solubility studies, solid complexes prepared by freeze drying method in 1:1 molar ratio were selected and characterized by DSC for confirmation of complex formation. Prepared solid dispersions were evaluated for drug content, solubility and in vitro dissolution. The physical stability of optimized formulation was studied at refrigerated and room temperature for 2 months. Solid state characterization of optimized complex performed by DSC and XRD studies. Dissolution rate of isradipine was increased compared with pure drug and more with HP-β-CD inclusion complex than β-CD. DSC and XRD analyzes that drug was in amorphous form, when the drug was incorporated as isradipine β-CD and HP-β-CD inclusion complex. Stability studies resulted in low or no variations in the percentage of complexation efficiency suggesting good stability of molecular complexes. The results conclusively demonstrated that the enhancement of solubility and dissolution rate of isradipine by drug-cyclodextrin complexation was achieved.

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The reductive dissolution of synthetic goethite and hematite in dithionite

Clay Minerals ◽

10.1180/claymin.1987.022.3.07 ◽

1987 ◽

Vol 22 (3) ◽

pp. 329-337 ◽

Cited By ~ 83

Author(s):

J. Torrent ◽

U. Schwertmann ◽

V. Barron

Keyword(s):

Specific Surface ◽

Dissolution Rate ◽

Surface Area ◽

Reductive Dissolution ◽

Natural Environments ◽

Dissolution Rates ◽

Aluminium Substitution ◽

Initial Dissolution Rate

AbstractThe reductive dissolution by Na-dithionite of 28 synthetic goethites and 26 hematites having widely different crystal morphologies, specific surfaces and aluminium substitution levels has been investigated. For both minerals the initial dissolution rate per unit of surface area decreased with aluminium substitution. At similar aluminium substitution and specific surface, goethites and hematites showed similar dissolution rates. These results suggest that preferential, reductive dissolution of hematite in some natural environments, such as soils or sediments, might be due to the generally lower aluminium substitution of this mineral compared to goethite.

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STUDIES ON UREA CO-INCLUSION COMPLEXES OF EBASTINE FOR STEEP IMPROVEMENT IN DISSOLUTION PROFILE

INDIAN DRUGS ◽

10.53879/id.54.08.10669 ◽

2017 ◽

Vol 54 (08) ◽

pp. 35-45

Author(s):

M. Dhall ◽

◽

A. K. Madan

Keyword(s):

Dissolution Rate ◽

Release Kinetics ◽

Thermal Studies ◽

Physical Stability ◽

Molar Fraction ◽

Aqueous Solubility ◽

Weibull Model ◽

Complexing Agent ◽

Content Uniformity ◽

Dissolution Profile

Urea co-inclusion technique has been successfully utilized for steep enhancement in dissolution rate of ebastine (EB), a BCS class II potent drug. EB is a novel second generation H1 receptor antagonist used for prevention of chronic idiopathic urticaria and allergic rhinitis. It exhibits low aqueous solubility and consequent poor bioavailability. In the present study, EB was engulfed in urea channel/tunnels along with rapidly complexing agent (RCA). Resulting complexes of EB (EBUCIC) were characterized by DSC, FTIR, XRD and 1H-NMR. Minimum proportion of RCA for incorporation of EB in hexagonal urea was determined calorimetrically. The thermal studies indicated increase in heat of decomposition with increasing molar fraction of RCA in EBUCICs, ensuring better physical stability of complexes. Content uniformity study depicted uniform composition formulation of EB. Weibull model described release kinetics of EB. Enhancement in dissolution rate ensures urea co-inclusion to be a useful approach for development of rapid/instantaneous release dosage forms.

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The Role of Functional Excipients in Solid Oral Dosage Forms to Overcome Poor Drug Dissolution and Bioavailability

Pharmaceutics ◽

10.3390/pharmaceutics12050393 ◽

2020 ◽

Vol 12 (5) ◽

pp. 393 ◽

Cited By ~ 3

Author(s):

Jannes van der Merwe ◽

Jan Steenekamp ◽

Dewald Steyn ◽

Josias Hamman

Keyword(s):

Dissolution Rate ◽

Solid Dispersions ◽

Aqueous Solubility ◽

Dosage Forms ◽

Oral Dosage ◽

Drug Dissolution ◽

Specific Reference ◽

Dissolution Rates ◽

Bioavailability Enhancement ◽

Poor Solubility

Many active pharmaceutical ingredients (APIs) exhibit poor solubility and low dissolution rates in aqueous environments such as the luminal fluids of the gastrointestinal tract. The oral bioavailability of these compounds is usually very low as a result of their poor solubility properties. In order to improve the bioavailability of these poorly soluble drugs, formulation strategies have been applied as a means to improve their aqueous solubility and dissolution rates. With respect to formulation approaches, excipients can be incorporated in the formulation to assist in the dissolution process of the drug, or specialized dosage forms can be formulated that improve dissolution rate through various mechanisms. This paper provides an overview of selected excipients (e.g., alkalinizing agents, surfactants and sugars) that can be used in formulations to increase the dissolution rate as well as specialized dosage forms such as self-emulsifying delivery systems and formulation techniques such as inclusion complexes and solid dispersions. These formulation approaches are discussed with available examples with specific reference to positive outcomes in terms of drug solubility and bioavailability enhancement.

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Molecular Dynamics and Physical Stability of Pharmaceutical Co-amorphous Systems: Correlation Between Structural Relaxation Times Measured by Kohlrausch-Williams-Watts With the Width of the Glass Transition Temperature (ΔTg) and the Onset of Crystallization

Journal of Pharmaceutical Sciences ◽

10.1016/j.xphs.2019.09.013 ◽

2019 ◽

Vol 108 (12) ◽

pp. 3848-3858 ◽

Cited By ~ 1

Author(s):

Norman Chieng ◽

XuJen Teo ◽

Min Hui Cheah ◽

Miao Ling Choo ◽

Jocelyn Chung ◽

...

Keyword(s):

Molecular Dynamics ◽

Glass Transition ◽

Transition Temperature ◽

Glass Transition Temperature ◽

Structural Relaxation ◽

Physical Stability ◽

Relaxation Times ◽

Amorphous Systems

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Discovery, Characterization, and Pharmaceutical Applications of Two Loratadine–Oxalic Acid Cocrystals

Crystals ◽

10.3390/cryst10110996 ◽

2020 ◽

Vol 10 (11) ◽

pp. 996

Author(s):

Zhengxuan Liang ◽

Hongbo Chen ◽

Chenguang Wang ◽

Changquan Calvin Sun

Keyword(s):

Oxalic Acid ◽

Dissolution Rate ◽

Physical Stability ◽

Formulation Development ◽

Intrinsic Dissolution ◽

Intrinsic Dissolution Rate ◽

Conjugate Acid ◽

Enhanced Solubility ◽

Antihistamine Drug ◽

Low Solubility

Loratadine (Lor) is an antihistamine drug commonly used to relieve the symptoms of allergy. It has high permeability but low solubility under physiological conditions. To overcome the problem of low solubility, we synthesized and characterized two Loratadine multi-component crystalline phases with oxalic acid (Oxa), i.e., a 1:1 Lor-Oxa conjugate acid-base (CAB) cocrystal (Lor-Oxa CAB) and a 2:1 Lor-Oxa cocrystal monohydrate (Lor-Oxa hydrate). Both cocrystals exhibited an enhanced solubility and intrinsic dissolution rate (IDR) compared to Lor and adequate physical stability. The intrinsic dissolution rate of Lor-Oxa CAB is 95 times that of Lor, which makes it a promising candidate for tablet formulation development.

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Comparison and Modeling of Aqueous Dissolution Rates of Various Uranium Oxides

MRS Proceedings ◽

10.1557/proc-465-557 ◽

1996 ◽

Vol 465 ◽

Cited By ~ 7

Author(s):

S. A. Steward ◽

E. T. Mones

Keyword(s):

Dissolution Rate ◽

Atmospheric Oxygen ◽

Fold Increase ◽

Stable Phase ◽

Uranium Oxides ◽

Spent Fuel ◽

Geologic Repository ◽

Dissolution Rates ◽

Intrinsic Dissolution ◽

Carbonate Concentration

ABSTRACTThe purpose of this work has been to measure and model the intrinsic dissolution rates of uranium oxides under a variety of well-controlled conditions that are relevant to a geologic repository. When exposed to air at elevated temperature, spent fuel may form the stable phase U3O8. Dehydrated schoepite, UO3H2O, has been shown to exist in drip tests on spent fuel.Equivalent sets of U3O8 and UO3H2 dissolution experiments allowed a systematic examination of the effects of temperature (25–75°C), pH (8–10) and carbonate (2–200×10−4 molar) concentrations at atmospheric oxygen conditions.Results indicate that UO3H2O has a much higher dissolution rate (at least ten-fold) than U3O8 under the same conditions. The intrinsic dissolution rate of unirradiated U3O8 is about twice that of UO2. Dissolution of both U3O8 and UO3.H2O shows a very high sensitivity to carbonate concentration. Present results show a 25 to 50-fold increase in room-temperature UO3H2O dissolution rates between the highest and lowest carbonate concentrations.As with the UO2 dissolution data the classical observed chemical kinetic rate law was used to model the U3O8 dissolution rate data. The pH did not have much effect on the models, in agreement with the earlier analysis of the UO2 and spent fuel dissolution data,. However, carbonate concentration, not temperature, had the strongest effect on the U3O8 dissolution rate. The U3O8 dissolution activation energy was about 6000 cal/mol, compared with 7300 and 8000 cal/mol for spent fuel and UO2 respectively.

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Uranium (iv) Dioxide and Simfuel as Chemical Analogues of Nuclear Spent Fuel Matrix Dissolution. A Comparison of Dissolution Results in a Standard Naci/NaHCO3 Solution

MRS Proceedings ◽

10.1557/proc-353-601 ◽

1994 ◽

Vol 353 ◽

Cited By ~ 16

Author(s):

Jordi Bruno ◽

I. Casas ◽

E. Cera ◽

J. de Pablo ◽

J. GimÉnez ◽

...

Keyword(s):

Dissolution Rate ◽

Nuclear Fuel ◽

Spent Nuclear Fuel ◽

Dissolution Process ◽

Experimental Comparison ◽

Comparison Study ◽

Spent Fuel ◽

Dissolution Rates ◽

Surface Sites ◽

Radiolytic Oxidation

AbstractWe have carried out an experimental comparison study of the dissolution rates of unirradiated UO2 and SIMFUEL pellets and particles (100–300 μm) in a standard NaCI/NaHC03 solution, under oxidizing conditions. We have performed the experiments using batch and flow methodologies. Both methodologies gave similar results, indicating that the overall oxidation/dissolution process is the same in both cases. The results from the experiments indicate that under these conditions the dissolution process is both oxygen and bicarbonate promoted. The dissolution rates we obtained are: R=2.4 ± 0.8 mg U/m2 d for U02 and R= 0.17 ± 0.05 mg U/m2 d for SIMFUEL. The results of the experiments indicate that the dissolution rate under oxic conditions is clearly dependent on the number of U(VI) surface sites which for spent nuclear fuel is a function of the extent of radiolytic oxidation.

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Common ion effect on solubility and dissolution rate of the sodium salt of an organic acid

Journal of Pharmacy and Pharmacology ◽

10.1111/j.2042-7158.1987.tb03434.x ◽

1987 ◽

Vol 39 (8) ◽

pp. 587-591 ◽

Cited By ~ 22

Author(s):

Abu T. M. Serajuddin ◽

Pai-Chang Sheen ◽

Matthew A. Augustine

Keyword(s):

Organic Acid ◽

Dissolution Rate ◽

Sodium Salt ◽

Common Ion ◽

Common Ion Effect

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A Kinetic Model for Borosilicate Glass Dissolution Based on the Dissolution Affinity of a Surface Alteration Layer

MRS Proceedings ◽

10.1557/proc-176-209 ◽

1989 ◽

Vol 176 ◽

Cited By ~ 60

Author(s):

William L. Bourcier ◽

Dennis W. Peiffer ◽

Kevin G. Knauss ◽

Kevin D. McKeegan ◽

David K. Smith

Keyword(s):

Kinetic Model ◽

Dissolution Rate ◽

Borosilicate Glass ◽

Geochemical Modeling ◽

Secondary Phases ◽

Dissolution Rates ◽

Ion Concentrations ◽

Glass Dissolution ◽

Gel Layer ◽

Amorphous Surface

ABSTRACTA kinetic model for the dissolution of borosilicate glass, incorporated into the EQ3/6 geochemical modeling code, is used to predict the dissolution rate of a nuclear waste glass. In the model, the glass dissolution rate is controlled by the rate of dissolution of an alkalidepleted amorphous surface (gel) layer. Assuming that the gel layer dissolution affinity controls glass dissolution rates is similar to the silica saturation concept of Grambow [1] except that our model predicts that all components concentrated in the surface layer, not just silica, affect glass dissolution rates. The good agreement between predicted and observed elemental dissolution rates suggests that the dissolution rate of the gel layer limits the overall rate of glass dissolution. The model predicts that the long-term rate of glass dissolution will depend mainly on ion concentrations in solution, and therefore on the secondary phases which precipitate and control ion concentrations.

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