Increasing Dissolution Rates and Gastrointestinal Absorption of Drugs via solid Solutions and Eutectic mixtures II

Goldberg, Arthur H.; Gibaldi, Milo; Kanig, Joseph L.

doi:10.1002/jps.2600550507

Cited by 126 publications

(53 citation statements)

References 7 publications

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“…On the contrary, another study reported that the drug need not exist in a microcrystalline state; a certain fraction of the drug may be molecularly dispersed in the matrix, forming solid solution [11] . When a solid dispersion is dispersed in aqueous medium, the carrier solubilised and released the drug as fine colloidal particles, leading to the enhancement of dissolution rate and bioavailability of poorly water-soluble drugs which could be attributed to enhanced surface area [5] .…”

Section: Review Articlementioning

confidence: 99%

Enhancement of the Solubility of Poorly Water Soluble Drugs through Solid Dispersion: A Comprehensive Review

Singh¹,

Kaur²,

Gupta³

et al. 2017

pharmaceutical-sciences

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Absorption of a drug through the oral route involves its dissolution from the formulation into gastric and/ or intestinal fluids followed by its permeation through gastrointestinal cell membranes and finally into the systemic circulation. Oral solid dosage forms are one of the most commonly used formulation types having multiple benefits over other formulations/routes. However, the challenge for a pharmaceutical scientist lies in the fact that dissolution of a drug from an oral solid formulation (a key factor in drug absorption) is dependent on the aqueous solubility of the drug. Therefore, a drug with poor aqueous solubility would exhibit dissolution rate limited absorption and similarly a drug possessing poor membrane permeability undergo permeation rate limited absorption. A drug is highly soluble when highest dose of drug is soluble in ≤250 ml of water over a pH range of 1 to 7.5 and a drug is highly permeable when extent of absorption in humans is to be ≥90% of an administered dose [1] . It has been investigated that most of new chemical entities currently being discovered and intended to be used as a solid dosage form should produce an efficient and reproducible plasma concentration after oral administration. However, most of them tend to have poor water solubility, which limits the therapeutic efficacy of that drug. Moreover, poor solubility results in increased dose and frequent administration leading to higher incidences of side-effects [2][3][4][5][6] . Hence, pharmaceutical research has emphasised on elevating the oral bioavailability of poorly water-soluble drugs by improving their solubility, dissolution rate and membrane permeability. Solubility is an important determinant in drug liberation and hence drug absorption, which plays a key role in oral bioavailability of formulations. The dissolution rate of a drug directly depends upon its solubility. Most of the new drugs have poor water solubility; thereby pose a difficulty in formulating into drug delivery systems. Therefore, solubility enhancement of poorly water soluble drugs is one of the necessary preformulation steps in the pharmaceutical product development research. Solid dispersion is a unique and promising approach for enhancing the dissolution characteristics and oral bioavailability of poorly water-soluble drugs. The present review highlights portrayal of solid dispersions, its types including eutectic mixtures and solid solutions, method of preparation and also the useful carriers for the preparation of solid dispersions. Furthermore, the wide research conducted hitherto on solid dispersions for enhancing solubility of different efficacious drugs, challenges encountered in the development of solid dispersions and recent advancements to overcome its pitfalls have also been elaborated.

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Section: Review Articlementioning

confidence: 99%

Enhancement of the Solubility of Poorly Water Soluble Drugs through Solid Dispersion: A Comprehensive Review

Singh¹,

Kaur²,

Gupta³

et al. 2017

pharmaceutical-sciences

View full text Add to dashboard Cite

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“…The formation of eutectic mixture is usually governed by the following factors: (a) the compounds must be miscible in their liquid state and immiscible in their solid state (2), (b) intimate physical interaction between eutectic-forming compounds is necessary for contact-induced melting point depression (3), and (c) the compounds should have chemical groups that can interact to form physical bonds such as intermolecular hydrogen bonding. Eutectic mixtures can be formed between active pharmaceutical ingredients (APIs), APIs and excipients, or between excipients; thereby, providing a vast scope for their application in the pharmaceutical industry (4)(5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Characterization and Comparison of Lidocaine-Tetracaine and Lidocaine-Camphor Eutectic Mixtures Based on Their Crystallization and Hydrogen-Bonding Abilities

et al. 2014

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Abstract. Eutectic mixtures formed between active pharmaceutical ingredients and/or excipients provide vast scope for pharmaceutical applications. This study aimed at the exploration of the crystallization abilities of two eutectic mixtures (EM) i.e., lidocaine-tetracaine and lidocaine-camphor (1:1 w/w). Thermogravimetric analysis (TGA) for degradation behavior whereas modulated temperature differential scanning calorimetry (MTDSC) set in first heating, cooling, and second heating cycles, was used to qualitatively analyze the complex exothermic and endothermic thermal transitions. Raman microspectroscopy characterized vibrational information specific to chemical bonds. Prepared EMs were left at room temperature for 24 h to visually examine their crystallization potentials. The degradation of lidocaine, tetracaine, camphor, lidocaine-tetracaine EM, and lidocaine-camphor EM began at 196.56, 163.82, 76.86, 146.01, and 42.72°C, respectively, which indicated that eutectic mixtures are less thermostable compared to their individual components. The MTDSC showed crystallization peaks for lidocaine, tetracaine, and camphor at 31.86, 29.36, and 174.02°C, respectively (n=3). When studying the eutectic mixture, no crystallization peak was observed in the lidocaine-tetracaine EM, but a lidocaine-camphor EM crystallization peak was present at 18.81°C. Crystallization occurred in lidocaine-camphor EM after being kept at room temperature for 24 h, but not in lidocaine-tetracaine EM. Certain peak shifts were observed in Raman spectra which indicated possible interactions of eutectic mixture components, when a eutectic mixture was formed. We found that if the components forming a eutectic mixture have crystallization peaks close to each other and have sufficient hydrogen-bonding capability, then their eutectic mixture is least likely to crystallize out (as seen in lidocaine-tetracaine EM) or vice versa (lidocainecamphor EM).

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“…Because of the greater stability, smaller bulk, accurate dosage and easy production, solid dosage forms have many advantages over other types of oral dosage forms. Therefore, most of the new chemical entities under development these days are intended to be used as a solid dosage form that originate an effective reproducible in vivo plasma concentration after oral administration 3,4 . In fact, most new chemical entities are poorly soluble drugs, not wellabsorbed after oral administration 4,5 , which can distract from the drug's inherent efficacy [6][7][8] .…”

Section: Introductionmentioning

confidence: 99%

Untitled

2010

IJPSR

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The solubility behavior of drugs remains one of the most challenging aspects in the formulation development. Although there was a great interest in solid dispersion systems during the past four decades to increase solubility by improving dissolution rate and bioavailability of poorly soluble drugs; there commercial use has been very limited, primarily because of manufacturing difficulties and various stability problems. It can be carried out by reducing drug particle size to the absolute minimum, and hence improving drug wet-ability, bioavailability may be significantly improved. Solid dispersion of drugs was generally produced by melt or solvent evaporation methods. Recently, surfactants have been included to stabilize the formulations, thus avoiding drug recrystallization and potentiating their solubility. New manufacturing processes to obtain solid dispersions have also been developed to reduce the drawbacks of the initial process. In this review, it is intended to discuss the eminent approach to improve the solubility or the dissolution rate and recent revival has been discussed.

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Increasing Dissolution Rates and Gastrointestinal Absorption of Drugs via solid Solutions and Eutectic mixtures II

Cited by 126 publications

References 7 publications

Enhancement of the Solubility of Poorly Water Soluble Drugs through Solid Dispersion: A Comprehensive Review

Enhancement of the Solubility of Poorly Water Soluble Drugs through Solid Dispersion: A Comprehensive Review

Characterization and Comparison of Lidocaine-Tetracaine and Lidocaine-Camphor Eutectic Mixtures Based on Their Crystallization and Hydrogen-Bonding Abilities

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