Pharmaceutics

1134 KiB

Open AccessArticle

Formulation and in Vitro, ex Vivo and in Vivo Evaluation of Elastic Liposomes for Transdermal Delivery of Ketorolac Tromethamine

by Guadalupe Nava, Elizabeth Piñón, Luis Mendoza, Néstor Mendoza, David Quintanar and Adriana Ganem

Pharmaceutics 2011, 3(4), 954-970; https://doi.org/10.3390/pharmaceutics3040954 - 15 Dec 2011

Cited by 71 | Viewed by 10460

Abstract

The objective of the current study was to formulate ketorolac tromethamine-loaded elastic liposomes and evaluate their in vitro drug release and their ex vivo and in vivo transdermal delivery. Ketorolac tromethamine (KT), which is a potent analgesic, was formulated in elastic liposomes using [...] Read more.

The objective of the current study was to formulate ketorolac tromethamine-loaded elastic liposomes and evaluate their in vitro drug release and their ex vivo and in vivo transdermal delivery. Ketorolac tromethamine (KT), which is a potent analgesic, was formulated in elastic liposomes using Tween 80 as an edge activator. The elastic vesicles were prepared by film hydration after optimizing the sonication time and number of extrusions. The vesicles exhibited an entrapment efficiency of 73 ± 11%, vesicle size of 127.8 ± 3.4 nm and a zeta potential of −12 mV. In vitro drug release was analyzed from liposomes and an aqueous solution, using Franz diffusion cells and a cellophane dialysis membrane with molecular weight cut-off of 8000 Da. Ex vivo permeation of KT across pig ear skin was studied using a Franz diffusion cell, with phosphate buffer (pH 7.4) at 32 °C as receptor solution. An in vivo drug permeation study was conducted on healthy human volunteers using a tape-stripping technique. The in vitro results showed (i) a delayed release when KT was included in elastic liposomes, compared to an aqueous solution of the drug; (ii) a flux of 0.278 mg/cm²h and a lag time of about 10 h for ex vivo permeation studies, which may indicate that KT remains in the skin (with the possibility of exerting a local effect) before reaching the receptor medium; (iii) a good correlation between the total amount permeated, the penetration distance (both determined by tape stripping) and transepidermal water loss (TEWL) measured during the in vivo permeation studies. Elastic liposomes have the potential to transport the drug through the skin, keep their size and drug charge, and release the drug into deep skin layers. Therefore, elastic liposomes hold promise for the effective topical delivery of KT. Full article

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931 KiB

Open AccessReview

Ionic Channels as Targets for Drug Design: A Review on Computational Methods

by Gregorio Fernández-Ballester, Asia Fernández-Carvajal, José Manuel González-Ros and Antonio Ferrer-Montiel

Pharmaceutics 2011, 3(4), 932-953; https://doi.org/10.3390/pharmaceutics3040932 - 09 Dec 2011

Cited by 25 | Viewed by 9220

Abstract

Ion channels are involved in a broad range of physiological and pathological processes. The implications of ion channels in a variety of diseases, including diabetes, epilepsy, hypertension, cancer and even chronic pain, have signaled them as pivotal drug targets. Thus far, drugs targeting [...] Read more.

Ion channels are involved in a broad range of physiological and pathological processes. The implications of ion channels in a variety of diseases, including diabetes, epilepsy, hypertension, cancer and even chronic pain, have signaled them as pivotal drug targets. Thus far, drugs targeting ion channels were developed without detailed knowledge of the molecular interactions between the lead compounds and the target channels. In recent years, however, the emergence of high-resolution structures for a plethora of ion channels paves the way for computer-assisted drug design. Currently, available functional and structural data provide an attractive platform to generate models that combine substrate-based and protein-based approaches. In silico approaches include homology modeling, quantitative structure-activity relationships, virtual ligand screening, similarity and pharmacophore searching, data mining, and data analysis tools. These strategies have been frequently used in the discovery and optimization of novel molecules with enhanced affinity and specificity for the selected therapeutic targets. In this review we summarize recent applications of in silico methods that are being used for the development of ion channel drugs. Full article

(This article belongs to the Special Issue Drug Design and Targeting)

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199 KiB

Open AccessArticle

Effect of Duration and Amplitude of Direct Current when Lidocaine Is Delivered by Iontophoresis

by Susan A. Saliba, Courtney L. Teeter-Heyl, Patrick McKeon, Christopher D. Ingeroll and Ethan N. Saliba

Pharmaceutics 2011, 3(4), 923-931; https://doi.org/10.3390/pharmaceutics3040923 - 06 Dec 2011

Cited by 6 | Viewed by 6910

Abstract

Dosage for the galvanic stimulation for iontophoresis varies. Clinicians manipulate the duration or the amplitude of the current, but it is not known which is more effective. We compared the anesthetic effect of lidocaine HCL (2%) by manipulating the current parameters on 21 [...] Read more.

Dosage for the galvanic stimulation for iontophoresis varies. Clinicians manipulate the duration or the amplitude of the current, but it is not known which is more effective. We compared the anesthetic effect of lidocaine HCL (2%) by manipulating the current parameters on 21 healthy volunteers (age: 21.2 ± 4.2, height 170.7 ± 10.2 cm, mass 82.1 ± 19.2 kg). Three conditions were administered in a random order using a Phoresor II^® with 2 mL, 2% lidocaine HCL in an iontophoresis electrode. (1) HASD (40 mA_*min): High amplitude (4 mA), short duration (10 min); (2) LALD (40 mA^.min): Low amplitude (2 mA), long duration (20 min); (3) Sham condition (0 mA, 20 min). Semmes-Weinstein monofilament (SWM) scores were taken pre and post intervention to measure sensation changes. Two-way ANOVA with repeated measures was used to compare sensation. Both iontophoresis treatments: LALD (4.2 ± 0.32 mm) and HASD (4.2 ± 0.52 mm) significantly increased SWM scores, indicating an increase in anesthesia, compared to the sham condition (3.6 ± 0.06 mm) p < 0.05. Neither LALD nor HASD was more effective and there was no difference in anesthesia with the sham. Lidocaine delivered via iontophoresis reduces cutaneous sensation. However, there was no benefit in either a HASD or LALD treatment. Full article

(This article belongs to the Special Issue Transdermal Drug Delivery)

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193 KiB

Open AccessArticle

Formulation Patents and Dermatology and Obviousness

by Dan-Feng Mei, Josephine Liu and Michael A. Davitz

Pharmaceutics 2011, 3(4), 914-922; https://doi.org/10.3390/pharmaceutics3040914 - 21 Nov 2011

Viewed by 6854

Abstract

Most patents covering dermatologic products contain patent claims directed to the pharmaceutical formulation of the product. Such patents, known as formulation patents, are vulnerable to attacks based on the legal argument that the formulations covered are obvious over formulations already known prior to [...] Read more.

Most patents covering dermatologic products contain patent claims directed to the pharmaceutical formulation of the product. Such patents, known as formulation patents, are vulnerable to attacks based on the legal argument that the formulations covered are obvious over formulations already known prior to the filing of the patent application. Because obviousness is an important concept in patent law, recent court cases concerning obviousness and formulation patents were examined and discussed below. Courts have ruled that patent claims are obvious when features of the claimed formulation are found in the prior art, even if the features or characteristics of the formulation are not explicitly disclosed in the prior art. However, patentees have successfully overcome obviousness challenges where there were unexpected results or properties and/or the prior art taught away from the claimed invention. Full article

(This article belongs to the Special Issue Transdermal Drug Delivery)

531 KiB

Open AccessReview

Pharmacokinetic Drug Interactions of Antimicrobial Drugs: A Systematic Review on Oxazolidinones, Rifamycines, Macrolides, Fluoroquinolones, and Beta-Lactams

by Mathieu S. Bolhuis, Prashant N. Panday, Arianna D. Pranger, Jos G. W. Kosterink and Jan-Willem C. Alffenaar

Pharmaceutics 2011, 3(4), 865-913; https://doi.org/10.3390/pharmaceutics3040865 - 18 Nov 2011

Cited by 39 | Viewed by 14073

Abstract

Like any other drug, antimicrobial drugs are prone to pharmacokinetic drug interactions. These drug interactions are a major concern in clinical practice as they may have an effect on efficacy and toxicity. This article provides an overview of all published pharmacokinetic studies on [...] Read more.

Like any other drug, antimicrobial drugs are prone to pharmacokinetic drug interactions. These drug interactions are a major concern in clinical practice as they may have an effect on efficacy and toxicity. This article provides an overview of all published pharmacokinetic studies on drug interactions of the commonly prescribed antimicrobial drugs oxazolidinones, rifamycines, macrolides, fluoroquinolones, and beta-lactams, focusing on systematic research. We describe drug-food and drug-drug interaction studies in humans, affecting antimicrobial drugs as well as concomitantly administered drugs. Since knowledge about mechanisms is of paramount importance for adequate management of drug interactions, the most plausible underlying mechanism of the drug interaction is provided when available. This overview can be used in daily practice to support the management of pharmacokinetic drug interactions of antimicrobial drugs. Full article

(This article belongs to the Special Issue Drug Interactions of Antimicrobial Agents)

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1107 KiB

Open AccessArticle

Exploring the Correlation Between Lipid Packaging in Lipoplexes and Their Transfection Efficacy

by Behfar Moghaddam, Sarah E. McNeil, Qinguo Zheng, Afzal R. Mohammed and Yvonne Perrie

Pharmaceutics 2011, 3(4), 848-864; https://doi.org/10.3390/pharmaceutics3040848 - 18 Nov 2011

Cited by 24 | Viewed by 9699

Abstract

Whilst there is a large body of evidence looking at the design of cationic liposomes as transfection agents, correlates of formulation to function remain elusive. In this research, we investigate if lipid packaging can give further insights into transfection efficacy. DNA lipoplexes composed [...] Read more.

Whilst there is a large body of evidence looking at the design of cationic liposomes as transfection agents, correlates of formulation to function remain elusive. In this research, we investigate if lipid packaging can give further insights into transfection efficacy. DNA lipoplexes composed of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) in combination with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or 1,2-stearoyl-3-trimethylammonium-propane (DSTAP) were prepared by the lipid hydration method. Each of the formulations was prepared by hydration in dH₂O or phosphate buffer saline (PBS) to investigate the effect of buffer salts on lipoplex physicochemical characteristics and in vitro transfection. In addition, Langmuir monolayer studies were performed to investigate any possible correlation between lipid packaging and liposome attributes. Using PBS, rather than dH₂O, to prepare the lipoplexes increased the size of vesicles in most of formulations and resulted in variation in transfection efficacies. However, one combination of lipids (DSPE:DOTAP) could not form liposomes in PBS, whilst the DSPE:DSTAP combination could not form liposomes in either aqueous media. Monolayer studies demonstrated saturated lipid combinations offered dramatically closer molecular packing compared to the other combinations which could suggest why this lipid combination could not form vesicles. Of the lipoplexes prepared, those formulated with DSTAP showed higher transfection efficacy, however, the effect of buffer on transfection efficiency was formulation dependent. Full article

(This article belongs to the Special Issue Gene Therapy)

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1004 KiB

Open AccessArticle

Formulation Optimization of Sustained-Release Ammonio Methacrylate Copolymer Microspheres. Effects of Log P and Concentration of Polar Cosolvents, and Role of the Drug/Copolymer Ratio

by Péter Sipos, Róbert Rajkó, Klára Pintye-Hódi, István Erős and Piroska Szabó-Révész

Pharmaceutics 2011, 3(4), 830-847; https://doi.org/10.3390/pharmaceutics3040830 - 10 Nov 2011

Cited by 5 | Viewed by 7408

Abstract

The objectives of this work were the formulation optimization of the preparation process parameters and to evaluate spray-dried sustained-release microspheres using ammonio methacrylate copolymer (AMC) as a polymer matrix. The effects of log P and the concentrations of the cosolvents (acetone, methyl ethyl [...] Read more.

The objectives of this work were the formulation optimization of the preparation process parameters and to evaluate spray-dried sustained-release microspheres using ammonio methacrylate copolymer (AMC) as a polymer matrix. The effects of log P and the concentrations of the cosolvents (acetone, methyl ethyl ketone and n-butyl acetate) and different drug/copolymer ratios as independent variables on the physicochemical parameters (the W₁/O emulsion viscosity, the microsphere production yield, the average particle size, the encapsulation efficiency) and the cumulative in vitro drug release as dependent variables were studied. The optimization was carried out on the basis of the 3³ factorial design study. The optimization process results showed that addition of polar cosolvents proved effective, linear relationships were observed between the independent and the dependent variables. The best conditions were achieved by microspheres prepared by using a low/medium cosolvent log P, cosolvent concentration of 25–50% v/v and a drug/copolymer ratio of 1:16. The microspheres ensured sustained release with Nernst and Baker-Lonsdale release profiles. Full article

(This article belongs to the Special Issue Microencapsulation Technology Applied to Pharmaceutics)

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3281 KiB

Open AccessReview

Encapsulation of Natural Polyphenolic Compounds; a Review

by Aude Munin and Florence Edwards-Lévy

Pharmaceutics 2011, 3(4), 793-829; https://doi.org/10.3390/pharmaceutics3040793 - 04 Nov 2011

Cited by 656 | Viewed by 34689

Abstract

Natural polyphenols are valuable compounds possessing scavenging properties towards radical oxygen species, and complexing properties towards proteins. These abilities make polyphenols interesting for the treatment of various diseases like inflammation or cancer, but also for anti-ageing purposes in cosmetic formulations, or for nutraceutical [...] Read more.

Natural polyphenols are valuable compounds possessing scavenging properties towards radical oxygen species, and complexing properties towards proteins. These abilities make polyphenols interesting for the treatment of various diseases like inflammation or cancer, but also for anti-ageing purposes in cosmetic formulations, or for nutraceutical applications. Unfortunately, these properties are also responsible for a lack in long-term stability, making these natural compounds very sensitive to light and heat. Moreover, polyphenols often present a poor biodisponibility mainly due to low water solubility. Lastly, many of these molecules possess a very astringent and bitter taste, which limits their use in food or in oral medications. To circumvent these drawbacks, delivery systems have been developed, and among them, encapsulation would appear to be a promising approach. Many encapsulation methods are described in the literature, among which some have been successfully applied to plant polyphenols. In this review, after a general presentation of the large chemical family of plant polyphenols and of their main chemical and biological properties, encapsulation processes applied to polyphenols are classified into physical, physico-chemical, chemical methods, and other connected stabilization methods. After a brief description of each encapsulation process, their applications to polyphenol encapsulation for pharmaceutical, food or cosmetological purposes are presented. Full article

(This article belongs to the Special Issue Microencapsulation Technology Applied to Pharmaceutics)

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494 KiB

Open AccessArticle

Role of P-Glycoprotein Expression and Function in Cystinotic Renal Proximal Tubular Cells

by Karen Peeters, Martijn J. Wilmer, Joost P. Schoeber, Dorien Reijnders, Lambertus P. van den Heuvel, Rosalinde Masereeuw and Elena Levtchenko

Pharmaceutics 2011, 3(4), 782-792; https://doi.org/10.3390/pharmaceutics3040782 - 27 Oct 2011

Cited by 10 | Viewed by 6602

Abstract

P-glycoprotein (P-gp) is an ATP-dependent transporter localized at the apical membrane of the kidney proximal tubules, which plays a role in the efflux of cationic and amphipathic endogenous waste products and xenobiotics, such as drugs, into urine. Studies in mice deficient in P-gp [...] Read more.

P-glycoprotein (P-gp) is an ATP-dependent transporter localized at the apical membrane of the kidney proximal tubules, which plays a role in the efflux of cationic and amphipathic endogenous waste products and xenobiotics, such as drugs, into urine. Studies in mice deficient in P-gp showed generalized proximal tubular dysfunction similar to the phenotype of patients with cystinosis, an autosomal recessive disorder caused by mutations in the lysosomal cystine transporter cystinosin. Renal disease in cystinosis is characterized by generalized dysfunction of the apical proximal tubular influx transporters (so-called renal Fanconi syndrome) developing during infancy and gradually progressing towards end-stage renal disease before the 10th birthday in the majority of patients that are not treated with the cystine-depleting drug cysteamine. Here, we investigated whether the proximal tubular efflux transporter P-gp is affected in cystinosis and whether this might contribute to the development of renal Fanconi syndrome. We used conditionally immortalized (ci) proximal tubular epithelial cells (ciPTEC) derived from cystinotic patients and healthy volunteers. P-gp-mediated transport was measured by using the P-gp substrate calcein-AM in the presence and absence of the P-gp-inhibitor PSC833. P-gp activity was normal in cystinotic cells as compared to controls. Additionally, the effect of cysteamine on P-gp transport activity and phosphate uptake was determined; demonstrating increased P-gp activity in cystinotic cells, and further decrease of proximal tubular phosphate uptake. This observation is compatible with the persistence of renal Fanconi syndrome in vivo under cysteamine therapy. In summary, P-gp expression and activity are normal in cystinotic ciPTEC, indicating that P-gp dysfunction is not involved in the pathogenesis of cystinosis. Full article

(This article belongs to the Special Issue Transporter-Mediated Drug Interactions)

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302 KiB

Open AccessReview

Antiretroviral Drug Interactions: Overview of Interactions Involving New and Investigational Agents and the Role of Therapeutic Drug Monitoring for Management

by R. Chris Rathbun and Michelle D. Liedtke

Pharmaceutics 2011, 3(4), 745-781; https://doi.org/10.3390/pharmaceutics3040745 - 21 Oct 2011

Cited by 38 | Viewed by 9415

Abstract

Antiretrovirals are prone to drug-drug and drug-food interactions that can result in subtherapeutic or supratherapeutic concentrations. Interactions between antiretrovirals and medications for other diseases are common due to shared metabolism through cytochrome P450 (CYP450) and uridine diphosphate glucuronosyltransferase (UGT) enzymes and transport by [...] Read more.

Antiretrovirals are prone to drug-drug and drug-food interactions that can result in subtherapeutic or supratherapeutic concentrations. Interactions between antiretrovirals and medications for other diseases are common due to shared metabolism through cytochrome P450 (CYP450) and uridine diphosphate glucuronosyltransferase (UGT) enzymes and transport by membrane proteins (e.g., p-glycoprotein, organic anion-transporting polypeptide). The clinical significance of antiretroviral drug interactions is reviewed, with a focus on new and investigational agents. An overview of the mechanistic basis for drug interactions and the effect of individual antiretrovirals on CYP450 and UGT isoforms are provided. Interactions between antiretrovirals and medications for other co-morbidities are summarized. The role of therapeutic drug monitoring in the detection and management of antiretroviral drug interactions is also briefly discussed. Full article

(This article belongs to the Special Issue Drug Interactions of Antimicrobial Agents)

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Graphical abstract

884 KiB

Open AccessArticle

Development of Re-Usable Yeast-Gellan Gum Micro-Bioreactors for Potential Application in Continuous Fermentation to Produce Bio-Ethanol

by Sook Mun Tan, Paul Wan Sia Heng and Lai Wah Chan

Pharmaceutics 2011, 3(4), 731-744; https://doi.org/10.3390/pharmaceutics3040731 - 17 Oct 2011

Cited by 14 | Viewed by 7789

Abstract

The objectives of this study were to investigate the feasibility of encapsulating yeast cells using gellan gum by an emulsification method and to evaluate the fermentation efficiency and the reusability of the micro-bioreactors produced. It was found that yeast cells could be successfully [...] Read more.

The objectives of this study were to investigate the feasibility of encapsulating yeast cells using gellan gum by an emulsification method and to evaluate the fermentation efficiency and the reusability of the micro-bioreactors produced. It was found that yeast cells could be successfully encapsulated to form relatively spherical micro-bioreactors with high specific surface area for mass transfer. Cell viability was found to be reduced by one log reduction after the emulsification process. The ethanol yield of the micro-bioreactors was comparable to that of free yeast in the first fermentation cycle. The micro-bioreactors remained intact and could be re-used up to 10 cycles of fermentation. Despite cell breakthrough, relatively high ethanol yields were obtained, indicating that the micro-bioreactors also functioned as regenerative reservoirs of yeast. Full article

(This article belongs to the Special Issue Microencapsulation Technology Applied to Pharmaceutics)

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315 KiB

Open AccessArticle

From Mini to Micro Scale—Feasibility of Raman Spectroscopy as a Process Analytical Tool (PAT)

by Markus Wirges, Joshua Müller, Péter Kása, Jr., Géza Regdon, Jr., Klára Pintye-Hódi, Klaus Knop and Peter Kleinebudde

Pharmaceutics 2011, 3(4), 723-730; https://doi.org/10.3390/pharmaceutics3040723 - 14 Oct 2011

Cited by 11 | Viewed by 7248

Abstract

Background: Active coating is an important unit operation in the pharmaceutical industry. The quality, stability, safety and performance of the final product largely depend on the amount and uniformity of coating applied. Active coating is challenging regarding the total amount of coating and [...] Read more.

Background: Active coating is an important unit operation in the pharmaceutical industry. The quality, stability, safety and performance of the final product largely depend on the amount and uniformity of coating applied. Active coating is challenging regarding the total amount of coating and its uniformity. Consequently, there is a strong demand for tools, which are able to monitor and determine the endpoint of a coating operation. In previous work, it was shown that Raman spectroscopy is an appropriate process analytical tool (PAT) to monitor an active spray coating process in a pan coater [1]. Using a multivariate model (Partial Least Squares—PLS) the Raman spectral data could be correlated with the coated amount of the API diprophylline. While the multivariate model was shown to be valid for the process in a mini scale pan coater (batch size: 3.5 kg cores), the aim of the present work was to prove the robustness of the model by transferring the results to tablets coated in a micro scale pan coater (0.5 kg). Method: Coating experiments were performed in both, a mini scale and a micro scale pan coater. The model drug diprophylline was coated on placebo tablets. The multivariate model, established for the process in the mini scale pan coater, was applied to the Raman measurements of tablets coated in the micro scale coater for six different coating levels. Then, the amount of coating, which was predicted by the model, was compared with reference measurements using UV spectroscopy. Results: For all six coating levels the predicted coating amount was equal to the amounts obtained by UV spectroscopy within the statistical error. Thus, it was possible to predict the total coating amount with an error smaller than 3.6%. The root mean squares of errors for calibration and prediction (root mean square of errors for calibration and prediction—RMSEC and RMSEP) were 0.335 mg and 0.392 mg, respectively, which means that the predictive power of the model is not dependent on the scale or the equipment. Conclusion: The scale-down experiment showed that it was possible to transfer the PLS model developed on a mini scale coater to a micro scale coater. Full article

(This article belongs to the Special Issue The 1st Electronic Conference on Pharmaceutical Science)

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3069 KiB

Open AccessArticle

Investigation of the Formation Process of Two Piracetam Cocrystals during Grinding

by Sönke Rehder, Marten Klukkert, Korbinian A. M. Löbmann, Clare J. Strachan, Albrecht Sakmann, Keith Gordon, Thomas Rades and Claudia S. Leopold

Pharmaceutics 2011, 3(4), 706-722; https://doi.org/10.3390/pharmaceutics3040706 - 12 Oct 2011

Cited by 57 | Viewed by 9395

Abstract

Cocrystal formation rates during dry grinding and liquid-assisted grinding were investigated by X-ray powder diffractometry and Raman spectroscopy. Two polymorphic forms of piracetam were used to prepare known piracetam cocrystals as model substances, i.e.,piracetam-citric acid and piracetam-tartaric acid cocrystals. Raman spectroscopy in [...] Read more.

Cocrystal formation rates during dry grinding and liquid-assisted grinding were investigated by X-ray powder diffractometry and Raman spectroscopy. Two polymorphic forms of piracetam were used to prepare known piracetam cocrystals as model substances, i.e.,piracetam-citric acid and piracetam-tartaric acid cocrystals. Raman spectroscopy in combination with principal component analysis was used to visualize the cocrystal formation pathways. During dry grinding, cocrystal formation appeared to progress via an amorphous intermediate stage, which was more evident for the piracetam-citric acid than for the piracetam-tartaric acid cocrystal. It was shown that liquid-assisted grinding led to faster cocrystal formation than dry grinding, which may be explained by the higher transformation rate due to the presence of liquid. The cocrystal formation rate did not depend on the applied polymorphic form of the piracetam and no polymorphic cocrystals were obtained. Full article

(This article belongs to the Special Issue Pharmaceutical Salts and Co-Crystals)

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777 KiB

Open AccessReview

Transporter-Mediated Drug–Drug Interactions with Oral Antidiabetic Drugs

by Sabine Klatt, Martin F. Fromm and Jörg König

Pharmaceutics 2011, 3(4), 680-705; https://doi.org/10.3390/pharmaceutics3040680 - 12 Oct 2011

Cited by 31 | Viewed by 8977

Abstract

Uptake transporters (e.g., members of the SLC superfamily of solute carriers) and export proteins (e.g., members of the ABC transporter superfamily) are important determinants for the pharmacokinetics of drugs. Alterations of drug transport due to concomitantly administered drugs that interfere with drug transport [...] Read more.

Uptake transporters (e.g., members of the SLC superfamily of solute carriers) and export proteins (e.g., members of the ABC transporter superfamily) are important determinants for the pharmacokinetics of drugs. Alterations of drug transport due to concomitantly administered drugs that interfere with drug transport may alter the kinetics of drug substrates. In vitro and in vivo studies indicate that many drugs used for the treatment of metabolic disorders and cardiovascular diseases (e.g., oral antidiabetic drugs, statins) are substrates for uptake transporters and export proteins expressed in the intestine, the liver and the kidney. Since most patients with type 2 diabetes receive more than one drug, transporter-mediated drug-drug interactions are important molecular mechanisms leading to alterations in oral antidiabetic drug pharmacokinetics with the risk of adverse drug reactions. This review focuses on uptake transporters of the SLCO/SLC21 (OATP) and SLC22 (OCT/OAT) family of solute carriers and export pumps of the ABC (ATP-binding cassette) transporter superfamily (especially P-glycoprotein) as well as the export proteins of the SLC47 (MATE) family and their role for transporter-mediated drug-drug interactions with oral antidiabetic drugs. Full article

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247 KiB

Open AccessArticle

Mucoadhesive Gels Designed for the Controlled Release of Chlorhexidine in the Oral Cavity

by Adamo Fini, Valentina Bergamante and Gian Carlo Ceschel

Pharmaceutics 2011, 3(4), 665-679; https://doi.org/10.3390/pharmaceutics3040665 - 27 Sep 2011

Cited by 61 | Viewed by 8913

Abstract

This study describes the in vitro/ex vivo buccal release of chlorhexidine (CHX) from nine mucoadhesive aqueous gels, as well as their physicochemical and mucoadhesive properties: CHX was present at a constant 1% w/v concentration in the chemical form of digluconate salt. The mucoadhesive/gel [...] Read more.

This study describes the in vitro/ex vivo buccal release of chlorhexidine (CHX) from nine mucoadhesive aqueous gels, as well as their physicochemical and mucoadhesive properties: CHX was present at a constant 1% w/v concentration in the chemical form of digluconate salt. The mucoadhesive/gel forming materials were carboxymethyl- (CMC), hydroxypropylmethyl- (HPMC) and hydroxypropyl- (HPC) cellulose, alone (3% w/w) or in binary mixtures (5% w/w); gels were tested for their mucoadhesion using the mucin method at 1, 2 and 3% w/w concentrations. CHX release from different formulations was assessed using a USP method and newly developed apparatus, combining release/permeation process in which porcine mucosa was placed in a Franz cell. The combination of HPMC or HPC with CMC showed slower drug release when compared to each of the individual polymers. All the systems proved suitable for CHX buccal delivery, being able to guarantee both prolonged release and reduced transmucosal permeation. Gels were compared for the release of previously studied tablets that contained Carbopol and HPMC, alone or in mixture. An accurate selection and combination of the materials allow the design of different pharmaceutical forms suitable for different purposes, by simply modifying the formulation compositions. Full article

(This article belongs to the Special Issue The Progress on Pharmaceutics in Drug Delayed Release System)

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Pharmaceutics, Volume 3, Issue 4 (December 2011) – 15 articles , Pages 665-970

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