Jonathan M Miller

Ben-Gurion University of the Negev, Beersheba, Southern District, Israel

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Publications (16)66.43 Total impact

  • Avital Beig, Jonathan M Miller, Arik Dahan
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    ABSTRACT: The purpose of this study was to investigate the interaction of 2-hydroxypropyl-β-cyclodextrin (HPβCD) and 2,6-dimethyl-β-cyclodextrin (DMβCD) with the lipophilic drug nifedipine, and to investigate the subsequent solubility-permeability interplay. Solubility curves of nifedipine with HPβCD and DMβCD in MES buffer were evaluated using phase solubility methods. Then, the apparent permeability of nifedipine was investigated as a function of increasing HPβCD/DMβCD concentration in the hexadecane-based PAMPA model. The interaction with nifedipine was CD dependent; significantly higher stability constant was obtained for DMβCD in comparison to HPβCD. Moreover, nifedipine displays different type of interaction with these CDs; a 1:1 stoichiometric inclusion complex was apparent with HPβCD, while 1:2 stoichiometry was apparent for DMβCD. In all cases, decreased apparent intestinal permeability of nifedipine as a function of increasing CD level and nifedipine apparent solubility was obtained. A quasi-equilibrium mass transport analysis was developed to explain this solubility-permeability interplay; the model enabled excellent quantitative prediction of nifedipine's permeability as a function of CD concentrations. This work demonstrates that when using CDs in solubility-enabling formulations, a trade-off exists between solubility increase and permeability decrease that must not be overlooked. This tradeoff was found to be independent of the type of CD-drug interaction. The transport model presented here can aid in striking the appropriate solubility-permeability balance in order to achieve optimal overall absorption.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 06/2013; · 3.15 Impact Factor
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    ABSTRACT: The purposes of this study were to assess the efficiency of different nifedipine amorphous solid dispersions (ASDs) in achieving and maintaining supersaturation and to investigate the solubility-permeability interplay when increasing the apparent solubility via ASD formulations. Spray-dried ASDs of nifedipine in three different hydrophilic polymers, hydroxypropyl methylcellulose acetate succinate (HPMC-AS), copovidone, and polyvinylpyrrolidone (PVP), were prepared and characterized by powder X-ray diffraction and differential scanning calorimetry. The ability of these formulations to achieve and maintain supersaturation over 24 h was assessed. Then, nifedipine's apparent intestinal permeability was investigated as a function of increasing supersaturation in the parallel artificial membrane permeability assay model and in the single-pass rat intestinal perfusion model. The efficiency of the different ASDs to achieve and maintain supersaturation of nifedipine was found to be highly polymer dependent; while a dispersion in HPMC-AS enabled supersaturation 20× that of the crystalline aqueous solubility, a dispersion in copovidone enabled 10×, and PVP allowed supersaturation of only 5× that of the crystalline solubility. Nifedipine flux across the intestine from supersaturated solutions was increased, and the apparent intestinal permeability was constant, irrespective of the degree of supersaturation or the polymer being used. In conclusion, while with other solubility-enabling approaches (e.g., surfactants, cyclodextrins, cosolvents), it is not enough to increase the apparent solubility, but to strike the optimal solubility-permeability balance, which limits the chances for successful drug delivery, the amorphous form emerges as a more advantageous strategy, in which higher apparent solubility (i.e., supersaturation) will be readily translated into higher drug flux and overall absorption.
    The AAPS Journal 12/2012; · 4.39 Impact Factor
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    ABSTRACT: Recently, we have revealed a trade-off between solubility increase and permeability decrease when solubility-enabling oral formulations are employed. We have shown this trade-off phenomenon to be ubiquitous, and to exist whenever the aqueous solubility is increased via solubilizing excipients, regardless if the mechanism involves decreased free fraction (cyclodextrins complexation, surfactant micellization) or simple cosolvent solubilization. Discovering a way to increase drug solubility without concomitant decreased permeability represents a major advancement in oral delivery of lipophilic drugs and is the goal of this work. For this purpose, we sought to elucidate the solubility-permeability interplay when increased apparent solubility is obtained via supersaturation from an amorphous solid dispersion (ASD) formulation. A spray-dried ASD of the lipophilic drug progesterone was prepared in the hydrophilic polymer hydroxypropyl methylcellulose acetate succinate (HPMC-AS), which enabled supersaturation up to 4× the crystalline drug's aqueous solubility (8 μg/mL). The apparent permeability of progesterone from the ASD in HPMC-AS was then measured as a function of increasing apparent solubility (supersaturation) in the PAMPA and rat intestinal perfusion models. In contrast to previous cases in which apparent solubility increases via cyclodextrins, surfactants, and cosolvents resulted in decreased apparent permeability, supersaturation via ASD resulted in no decrease in apparent permeability with increasing apparent solubility. As a result, overall flux increased markedly with increasing apparent solubility via ASD as compared to the other formulation approaches. This work demonstrates that supersaturation via ASDs has a subtle yet powerful advantage over other solubility-enabling formulation approaches. That is, increased apparent solubility may be achieved without the expense of apparent intestinal membrane permeability. Thus, supersaturation via ASDs presents a markedly increased opportunity to maximize overall oral drug absorption.
    Molecular Pharmaceutics 05/2012; · 4.57 Impact Factor
  • Jonathan M Miller, Arik Dahan
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    ABSTRACT: Although the extraordinary solubility advantage afforded by cyclodextrins has led to their widespread use as pharmaceutical solubilizers, several reports have emerged that cyclodextrins may also reduce the apparent permeability of the drug. With the purpose to investigate this solubility-permeability interplay, we have recently developed a mathematical mass transport model that quantitatively explains the impact of molecular complexation on the intestinal permeability. This model enabled excellent quantitative prediction of progesterone P(eff) as a function of HPβCD concentrations in several experimental methods. The purpose of the present study was to challenge the predictive capabilities of this mathematical model, assessing whether the model allows the prediction of literature permeability data, as a model validation method. The mass-transport model was applied to carbamazepine and hydrocortisone, and the predicted permeability (P(eff), P(m) and P(aq)) vs. HPβCD concentration were plotted. Excellent agreement was obtained between literature experimental permeability and the predicted P(eff) values for both compounds at all of the HPβCD concentrations tested. The presented validated model that considers the opposing effects of the formulation on the solubility and the permeability, can lead to a more efficient and intelligent use of molecular complexation strategies; the formulator will be able to a priori strike the optimal solubility-permeability balance to maximize and facilitate the overall oral drug absorption.
    International Journal of Pharmaceutics 03/2012; 430(1-2):388-91. · 3.99 Impact Factor
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    Arik Dahan, Jonathan M Miller
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    ABSTRACT: While each of the two key parameters of oral drug absorption, the solubility and the permeability, has been comprehensively studied separately, the relationship and interplay between the two have been largely ignored. For instance, when formulating a low-solubility drug using various solubilization techniques: what are we doing to the apparent permeability when we increase the solubility? Permeability is equal to the drug's diffusion coefficient through the membrane times the membrane/aqueous partition coefficient divided by the membrane thickness. The direct correlation between the intestinal permeability and the membrane/aqueous partitioning, which in turn is dependent on the drug's apparent solubility in the GI milieu, suggests that the solubility and the permeability are closely associated, exhibiting a certain interplay between them, and the current view of treating the one irrespectively of the other may not be sufficient. In this paper, we describe the research that has been done thus far, and present new data, to shed light on this solubility-permeability interplay. It has been shown that decreased apparent permeability accompanies the solubility increase when using different solubilization methods. Overall, the weight of the evidence indicates that the solubility-permeability interplay cannot be ignored when using solubility-enabling formulations; looking solely at the solubility enhancement that the formulation enables may be misleading with regards to predicting the resulting absorption, and hence, the solubility-permeability interplay must be taken into account to strike the optimal solubility-permeability balance, in order to maximize the overall absorption.
    The AAPS Journal 03/2012; 14(2):244-51. · 4.39 Impact Factor
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    ABSTRACT: We have recently reported the interplay between apparent aqueous solubility and intestinal membrane permeability, showing the trade-off between the two when using cyclodextrin- and surfactant-based systems as solubility-enabling formulations. In these cases, the decreased permeability could be attributed directly to decreased free fraction of drug due to the complexation/micellization inherent in these solubilization methods. The purpose of this study was to investigate the direct solubility-permeability interplay, using formulations in which complexation is not the mechanism for increased solubilization. The apparent aqueous solubility (S(aq)) and rat intestinal permeability (P(eff)) of the lipophilic drug progesterone were measured in systems containing various levels of the cosolvents propylene glycol and PEG-400, since this solubilization method does not involve decreased free fraction. Thermodynamic activity was maintained equivalent in all permeability studies (75% equilibrium solubility). Both cosolvents increased progesterone S(aq) in nonlinear fashion. Decreased P(eff) with increased S(aq) was observed, despite the constant thermodynamic activity, and the nonrelevance of free fraction. A mass-transport analysis was developed to describe this interplay. The model considers the effects of solubilization on the membrane permeability (P(m)) and the unstirred water layer (UWL) permeability (P(aq)), to predict the overall P(eff) dependence on S(aq). The analysis revealed that (1) the effective UWL thickness quickly decreases with ↑S(aq), such that P(aq) markedly increases with ↑S(aq); (2) the apparent membrane/aqueous partitioning decreases with ↑S(aq), thereby reducing the thermodynamic driving force for permeability such that ↓P(m) with ↑S(aq); (3) since ↑P(aq) and ↓P(m) with ↑S(aq), the UWL is shorted out and P(eff) becomes membrane control with ↑S(aq). The model enabled excellent quantitative prediction of P(eff) as a function of S(aq). This work demonstrates that a direct trade-off exists between the apparent solubility and permeability, which must be taken into account when developing solubility-enabling formulations to strike the optimal solubility-permeability balance, in order to maximize the overall oral absorption.
    Molecular Pharmaceutics 03/2012; 9(3):581-90. · 4.57 Impact Factor
  • Avital Beig, Jonathan M Miller, Arik Dahan
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    ABSTRACT: The purpose of this paper was to study the solubility-permeability interplay in formulation development for oral administration of poor aqueous solubility drugs. The apparent solubility of the lipophilic drug carbamazepine was measured in systems containing various levels of the co-solvent PEG-400. The corresponding permeability was then measured in the PAMPA assay and in the rat jejunal perfusion model. Thermodynamic activity was maintained equivalent in all permeability studies (50% saturation). PEG-400 increased carbamazepine solubility in a concentration-dependent fashion. Decreased carbamazepine intestinal permeability with increased apparent solubility was observed in both PAMPA and rat perfusion models. Additionally, we have shown that the intestinal absorption of carbamazepine is membrane-controlled, with essentially no effective barrier function of the unstirred water layer. A mass transport analysis was employed to describe the solubility-permeability interplay. It was shown that the increased solubility in the aqueous GI milieu reduced the apparent membrane/aqueous partitioning, thereby reducing the driving force for membrane permeability. The model enabled excellent quantitative prediction of the effective permeability as a function of the solubility. In conclusion, a direct tradeoff between solubility increase and permeability decrease has been shown, which has to be accounted for when developing oral formulation for lipophilic drugs.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 02/2012; 81(2):386-91. · 3.15 Impact Factor
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    ABSTRACT: Surfactants are routinely employed to increase the apparent aqueous solubility of poorly soluble drugs. Yet the impact of micellar solubilization on the intestinal membrane permeability of a lipophilic drug is often overlooked and poorly understood. In this work, the interplay between the apparent solubility increase and intestinal membrane permeability decrease that exists when surfactants are used as drug solubility enhancers is described. A quasi-equilibrium mechanistic mass transport analysis was developed and employed to describe the effect of micellar solubilization by sodium taurocholate (STC) and sodium lauryl sulfate (SLS) on the intestinal membrane permeability of the lipophilic drug progesterone. The model considers the effects of micellar solubilization on both the membrane permeability (P(m)) and the unstirred water layer (UWL) permeability (P(aq)), to predict the overall effective permeability (P(eff)) dependence on surfactant concentration (C(S)). The analysis reveals that (1) the effective UWL thickness (h(aq)) quickly decreases with increasing C(S) above the critical micelle concentration (CMC), such that P(aq) markedly increases with increasing C(S); (2) the free fraction of drug available for membrane permeation decreases with increasing C(S) above CMC, such that P(m) decreases with increasing C(S); and (3) P(aq) increases and P(m) decreases with increasing C(S) above CMC, consequently the UWL is effectively shorted out and the overall P(eff) tends toward membrane control with increasing C(S). The model enabled excellent quantitative prediction of the progesterone P(eff) as a function of C(S) in the rat jejunal perfusion model. This work demonstrates that a trade-off exists between micellar apparent solubility increase and permeability decrease that must be taken into account to strike the optimal solubility-permeability balance. The model presented in this work offers the formulation scientist a simple method for a priori prediction of this interplay, in order to maximize the overall oral absorption.
    Molecular Pharmaceutics 08/2011; 8(5):1848-56. · 4.57 Impact Factor
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    ABSTRACT: INTRODUCTION: Guanidino-containing compounds are well-known for their important biological roles in vivo. In a rational drug design process, the guanidino group is frequently adopted to mimic the arginine residue of the endogenous substrate and secure the affinity of the drug to the target. However, due to their inherent polarity and positive charge in the gastrointestinal tract, it is difficult for guanidino-containing compounds to be orally absorbed by passive diffusion. Hence, guanidino-containing compounds are frequently associated with low oral bioavailability. AREAS COVERED: In this review, we present the barriers and challenges toward the oral absorption of guanidino-containing compounds, provide an overview of the research that has been done so far in the area, and summarize recent advances and future directions in the mechanistic enhancement of the intestinal absorption of drugs containing the polar guanidino functionality. For instance, application of several different prodrug approaches, a novel recently developed ion-pairing strategy and the utilization of advanced formulations are discussed. EXPERT OPINION: While additional research is required to allow efficient and facile solutions to low oral bioavailability of guanidino-containing compounds, novel and exciting strategies have been developed in recent years. Although challenging, the development of a potent guanidino-containing compound into an orally administered drug is becoming an achievable target.
    Expert Opinion on Drug Metabolism &amp Toxicology 03/2011; 7(3):313-23. · 2.94 Impact Factor
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    ABSTRACT: A rapid method for the analysis of polyethylene glycol (PEG 400) in perfusate samples is presented. Because PEG 400 lacks a strong chromophore in the UV range, detection was accomplished using evaporative light scattering detection (ELSD). In order to optimize the ELSD signal performance for a volatile mobile phase, the chromatographic separation was optimized using aqueous normal phase conditions on a Cogent® Diamond Hydride column.
    Analytical methods 03/2011; 3(3):742-744. · 1.86 Impact Factor
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    ABSTRACT: The FDA classifies a drug substance as high-permeability when the fraction of dose absorbed (F(abs)) in humans is 90% or higher. This direct correlation between human permeability and F(abs) has been recently controversial, since the beta-blocker sotalol showed high F(abs) (90%) and low Caco-2 permeability. The purpose of this study was to investigate the scientific basis for this disparity between permeability and F(abs). The effective permeabilities (P(eff)) of sotalol and metoprolol, a FDA standard for the low/high P(eff) class boundary, were investigated in the rat perfusion model, in three different intestinal segments with pHs corresponding to the physiological pH in each region: (1) proximal jejunum, pH 6.5; (2) mid small intestine, pH 7.0; and (3) distal ileum, pH 7.5. Both metoprolol and sotalol showed pH-dependent permeability, with higher P(eff) at higher pH. At any given pH, sotalol showed lower permeability than metoprolol; however, the permeability of sotalol determined at pH 7.5 exceeded/matched metoprolol's at pH 6.5 and 7.0, respectively. Physicochemical analysis based on ionization, pK(a) and partitioning of these drugs predicted the same trend and clarified the mechanism behind these observed results. Experimental octanol-buffer partitioning experiments confirmed the theoretical curves. An oral dose of metoprolol has been reported to be completely absorbed in the upper small intestine; it follows, hence, that metoprolol's P(eff) value at pH 7.5 is not likely physiologically relevant for an immediate release dosage form, and the permeability at pH 6.5 represents the actual relevant value for the low/high permeability class boundary. Although sotalol's permeability is low at pH 6.5 and 7.0, at pH 7.5 it exceeds/matches the threshold of metoprolol at pH 6.5 and 7.0, most likely responsible for its high F(abs). In conclusion, we have shown that, in fact, there is no discrepancy between P(eff) and F(abs) in sotalol's absorption; the data emphasize that, if a compound has high fraction of dose absorbed, it will have high-permeability, not necessarily in the jejunum, but at some point along the relevant intestinal regions.
    Molecular Pharmaceutics 09/2010; · 4.57 Impact Factor
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    ABSTRACT: Physiologically based pharmacokinetic (PBPK) modeling tools have become an integral part of the modern drug discovery-development process. However, accurate PK prediction of enabling formulations of poorly soluble compounds by applying PBPK modeling has been very limited. This is because current PBPK models rely only on thermodynamic drug solubility inputs (e.g., pH-solubility profile) and give little consideration to the dynamic changes in apparent drug solubility (e.g., supersaturation) that occur during gastrointestinal (GI) transit of an enabling formulation of a water insoluble drug. Moreover, biorepresentative and predictive in vitro tools to measure formulation dependent solubility changes during GI transit remain underdeveloped. In this work, we have developed an in vitro dual pH-dilution method based on rat physiology to estimate the apparent drug concentration in solution along the GI tract during release from solubility enabling formulations. This simple dual pH-dilution method was evaluated using various solubility enabling formulations (i.e., cosolvent solution, amorphous solid dispersions) made using a model early development drug candidate with poor aqueous solubility. The in vitro drug concentration-time profiles from the enabling formulations were used as solubility inputs for PBPK modeling using GastroPlus software. This resulted in excellent predictions of the in vivo oral plasma concentration-time profiles, as compared to using the traditional inputs of thermodynamic pH-solubility profiles. In summary, this work describes a novel in vitro method for facile estimation of formulation dependent GI drug concentration-time profiles and demonstrates the utility of PBPK modeling for oral PK prediction of enabling formulations of poorly soluble drugs.
    Molecular Pharmaceutics 08/2010; · 4.57 Impact Factor
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    ABSTRACT: Antiviral drugs often suffer from poor intestinal permeability, preventing their delivery via the oral route. The goal of this work was to enhance the intestinal absorption of the low-permeability antiviral agents zanamivir heptyl ester (ZHE) and guanidino oseltamivir (GO) utilizing an ion-pairing approach, as a critical step toward making them oral drugs. The counterion 1-hydroxy-2-naphthoic acid (HNAP) was utilized to enhance the lipophilicity and permeability of the highly polar drugs. HNAP substantially increased the log P of the drugs by up to 3.7 log units. Binding constants (K(11(aq))) of 388 M(-1) for ZHE-HNAP and 2.91 M(-1) for GO-HNAP were obtained by applying a quasi-equilibrium transport model to double-reciprocal plots of apparent octanol-buffer distribution coefficients versus HNAP concentration. HNAP enhanced the apparent permeability (P(app)) of both compounds across Caco-2 cell monolayers in a concentration-dependent manner, as substantial P(app) (0.8-3.0 x 10(-6) cm/s) was observed in the presence of 6-24 mM HNAP, whereas no detectable transport was observed without counterion. Consistent with a quasi-equilibrium transport model, a linear relationship with slope near 1 was obtained from a log-log plot of Caco-2 P(app) versus HNAP concentration, supporting the ion-pair mechanism behind the permeability enhancement. In the rat jejunal perfusion assay, the addition of HNAP failed to increase the effective permeability (P(eff)) of GO. However, the rat jejunal permeability of ZHE was significantly enhanced by the addition of HNAP in a concentration-dependent manner, from essentially zero without HNAP to 4.0 x 10(-5) cm/s with 10 mM HNAP, matching the P(eff) of the high-permeability standard metoprolol. The success of ZHE-HNAP was explained by its >100-fold stronger K(11(aq)) versus GO-HNAP, making ZHE-HNAP less prone to dissociation and ion-exchange with competing endogenous anions and able to remain intact during membrane permeation. Overall, this work presents a novel approach to enable the oral delivery of highly polar antiviral drugs, and provides new insights into the underlying mechanisms governing the success or failure of the ion-pairing strategy to increase oral absorption.
    Molecular Pharmaceutics 08/2010; 7(4):1223-34. · 4.57 Impact Factor
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    ABSTRACT: A quasi-equilibrium mass transport analysis has been developed to quantitatively explain the solubility-permeability interplay that exists when using cyclodextrins as pharmaceutical solubilizers. The model considers the effects of cyclodextrins on the membrane permeability (P(m)) as well as the unstirred water layer (UWL) permeability (P(aq)), to predict the overall effective permeability (P(eff)) dependence on cyclodextrin concentration (C(CD)). The analysis reveals that: (1) UWL permeability markedly increases with increasing C(CD) since the effective UWL thickness quickly decreases with increasing C(CD); (2) membrane permeability decreases with increasing C(CD), as a result of the decrease in the free fraction of drug; and (3) since P(aq) increases and P(m) decreases with increasing C(CD), the UWL is effectively eliminated and the overall P(eff) tends toward membrane control, that is, P(eff) approximately P(m) above a critical C(CD). Application of this transport model enabled excellent quantitative prediction of progesterone P(eff) as a function of HP beta CD concentrations in PAMPA assay, Caco-2 transepithelial studies, and in situ rat jejunal-perfusion model. This work demonstrates that when using cyclodextrins as pharmaceutical solubilizers, a trade-off exists between solubility increase and permeability decrease that must not be overlooked; the transport model presented here can aid in striking the appropriate solubility-permeability balance in order to achieve optimal overall absorption.
    Journal of Pharmaceutical Sciences 06/2010; 99(6):2739-49. · 3.13 Impact Factor
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    Arik Dahan, Jonathan M Miller, Gordon L Amidon
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    ABSTRACT: The Biopharmaceutics Classification System (BCS) categorizes drugs into one of four biopharmaceutical classes according to their water solubility and membrane permeability characteristics and broadly allows the prediction of the rate-limiting step in the intestinal absorption process following oral administration. Since its introduction in 1995, the BCS has generated remarkable impact on the global pharmaceutical sciences arena, in drug discovery, development, and regulation, and extensive validation/discussion/extension of the BCS is continuously published in the literature. The BCS has been effectively implanted by drug regulatory agencies around the world in setting bioavailability/bioequivalence standards for immediate-release (IR) oral drug product approval. In this review, we describe the BCS scientific framework and impact on regulatory practice of oral drug products and review the provisional BCS classification of the top drugs on the global market. The Biopharmaceutical Drug Disposition Classification System and its association with the BCS are discussed as well. One notable finding of the provisional BCS classification is that the clinical performance of the majority of approved IR oral drug products essential for human health can be assured with an in vitro dissolution test, rather than empirical in vivo human studies.
    The AAPS Journal 10/2009; 11(4):740-6. · 4.39 Impact Factor
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    ABSTRACT: The aim of this research was to gain a mechanistic understanding of ion-pair mediated membrane transport of low-permeability drugs. Quasi-equilibrium mass transport analyses were developed to describe the ion-pair mediated octanol-buffer partitioning and hydrophobic membrane permeation of the model basic drug phenformin. Three lipophilic counterions were employed: p-toluenesulfonic acid, 2-naphthalenesulfonic acid, and 1-hydroxy-2-naphthoic acid (HNAP). Association constants and intrinsic octanol-buffer partition coefficients (Log P(AB)) of the ion-pairs were obtained by fitting a transport model to double reciprocal plots of apparent octanol-buffer distribution coefficients versus counterion concentration. All three counterions enhanced the lipophilicity of phenformin, with HNAP providing the greatest increase in Log P(AB), 3.7 units over phenformin alone. HNAP also enhanced the apparent membrane permeability of phenformin, 27-fold in the PAMPA model, and 4.9-fold across Caco-2 cell monolayers. As predicted from a quasi-equilibrium analysis of ion-pair mediated membrane transport, an order of magnitude increase in phenformin flux was observed per log increase in counterion concentration, such that log-log plots of phenformin flux versus HNAP concentration gave linear relationships. These results provide increased understanding of the underlying mechanisms of ion-pair mediated membrane transport, emphasizing the potential of this approach to enable oral delivery of low-permeability drugs.
    Journal of Controlled Release 04/2009; 137(1):31-7. · 7.63 Impact Factor

Publication Stats

220 Citations
66.43 Total Impact Points

Institutions

  • 2012–2013
    • Ben-Gurion University of the Negev
      • Faculty of Health Sciences
      Beersheba, Southern District, Israel
  • 2011
    • Abbott Laboratories
      North Chicago, Illinois, United States
  • 2009–2011
    • University of Michigan
      • Department of Pharmaceutical Sciences
      Ann Arbor, MI, United States
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States