Correlation of hydrotropic solubilization by urea with logD of drug molecules and utilization of this effect for topical formulations

Herbig, Michael E.; Evers, Dirk-Heinrich

doi:10.1016/j.ejpb.2013.06.022

Cited by 26 publications

(21 citation statements)

References 3 publications

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“…Results of the release study can be associated with drug properties. TFH is a hydrophobic substance with log P 5.9 (14), which slightly dissolves in water. Poloxamer 407 increases TFH solubility, though small solid particles might occur in hydrogel.…”

Section: In Vitro Drug Releasementioning

confidence: 99%

Topical antifungal bigels: Formulation, characterization and evaluation

et al. 2018

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Bigels with antifungal substances, ciclopirox olamine and terbinafine hydrochloride, were made of hydrogel (poloxamer 407 gel) and oleogel (polyethylene and liquid paraffin mixture). Prepared bigels were found physically stable at room temperature for six months and at least four months at 40 °C. Released amount of drug decreased when oleogel concentration in the formulation increased. Release test results depended on the insertion place of active substances. The amount of released substance was highest when ciclopirox olamine was incorporated in both phases in an equal quantity, and terbinafine hydrochloride in oleogel or in hydrogel. All formulations showed great inhibition of Microsporum canis. Thus, bigels with ciclopirox olamine and terbinafine hydrochloride are a promising dosage form for topical use.

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Section: In Vitro Drug Releasementioning

confidence: 99%

Topical antifungal bigels: Formulation, characterization and evaluation

et al. 2018

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“…All compounds with logD values between 2.0 and 4.5 showed a SEF more than 5 in 40% aqueous solutions of urea while with a logD value below 2 or above 5, SEF was less than 5. In some cases such as diclofenac and prednicarbate, SEF achieved a value that was more than 5 at 5% urea and more than 250 at 20% urea 69 .…”

Section: Hydrotropes As Drug Carriersmentioning

confidence: 97%

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2019

IJPSR

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Drug discovery and development plays a major role in the world and serves mankind. The major criteria to be considered and given importance in drug development is the solubility of a drug. Among all newly discovered chemical entities, about 40% of drugs fail to reach the market due to their poor aqueous solubility or lipophilicity. Poor solubility is not only a problem for formulation development and clinical testing but also an obstacle at the very beginning while screening new compounds for pharmacological activity. Nowadays oral route is considered as the preferred route of drug administration than other routes due to its convenience in terms of ease of administration and economy. The first requirement of drug which is supposed to be given by oral route is good aqueous solubility, as the poor solubility leads to low absorption, inadequate and variable bioavailability and also gastrointestinal mucosal toxicity. To prevent these crisis, several solubility enhancement techniques have been employed to enhance the solubility of poorly soluble drugs and hydrotropic solubilization is one of them. Besides, the advantage of certain properties like high selectivity, non-inflammability, environmentally friendly, easy availability and cost-effectiveness of hydrotropes makes this technique superior to other solubilization techniques. In the present review, an attempt has been made to discuss the hydrotropic solubilization technique and highlight the applications with this approach.

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“…Hydrotropes are frequently anionic aromatic (e.g., salicylate, benzoate) or non-aromatic compounds (e.g., citrate), but can also be neutral (e.g., urea; Herbig and Evers, 2013). Urea is widely used as a hydrotropic agent, as it was shown to enhance the aqueous solubility of many lipophilic drugs including diclofenac (250-fold), hydrochlorothiazide (74-fold), and many others (Coffman and Kildsig, 1996a,b).…”

Section: Introductionmentioning

confidence: 99%

Hydrotropic Solubilization of Lipophilic Drugs for Oral Delivery: The Effects of Urea and Nicotinamide on Carbamazepine Solubility–Permeability Interplay

et al. 2016

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Hydrotropy refers to increasing the water solubility of otherwise poorly soluble compound by the presence of small organic molecules. While it can certainly increase the apparent solubility of a lipophilic drug, the effect of hydrotropy on the drugs’ permeation through the intestinal membrane has not been studied. The purpose of this work was to investigate the solubility–permeability interplay when using hydrotropic drug solubilization. The concentration-dependent effects of the commonly used hydrotropes urea and nicotinamide, on the solubility and the permeability of the lipophilic antiepileptic drug carbamazepine were studied. Then, the solubility–permeability interplay was mathematically modeled, and was compared to the experimental data. Both hydrotropes allowed significant concentration-dependent carbamazepine solubility increase (up to ∼30-fold). A concomitant permeability decrease was evident both in vitro and in vivo (∼17-fold for nicotinamide and ∼9-fold for urea), revealing a solubility–permeability tradeoff when using hydrotropic drug solubilization. A relatively simplified simulation approach based on proportional opposite correlation between the solubility increase and the permeability decrease at a given hydrotrope concentration allowed excellent prediction of the overall solubility–permeability tradeoff. In conclusion, when using hydrotropic drug solubilization it is prudent to not focus solely on solubility, but to account for the permeability as well; achieving optimal solubility–permeability balance may promote the overall goal of the formulation to maximize oral drug exposure.

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Correlation of hydrotropic solubilization by urea with logD of drug molecules and utilization of this effect for topical formulations

Cited by 26 publications

References 3 publications

Topical antifungal bigels: Formulation, characterization and evaluation

Topical antifungal bigels: Formulation, characterization and evaluation

Untitled

Hydrotropic Solubilization of Lipophilic Drugs for Oral Delivery: The Effects of Urea and Nicotinamide on Carbamazepine Solubility–Permeability Interplay

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