Pharmaceutics

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Open AccessReview

Augmented Renal Clearance in Critical Illness: An Important Consideration in Drug Dosing

by Sherif Hanafy Mahmoud and Chen Shen

Pharmaceutics 2017, 9(3), 36; https://doi.org/10.3390/pharmaceutics9030036 - 16 Sep 2017

Cited by 104 | Viewed by 11267

Augmented renal clearance (ARC) is a manifestation of enhanced renal function seen in critically ill patients. The use of regular unadjusted doses of renally eliminated drugs in patients with ARC might lead to therapy failure. The purpose of this scoping review was to [...] Read more.

Augmented renal clearance (ARC) is a manifestation of enhanced renal function seen in critically ill patients. The use of regular unadjusted doses of renally eliminated drugs in patients with ARC might lead to therapy failure. The purpose of this scoping review was to provide and up-to-date summary of the available evidence pertaining to the phenomenon of ARC. A literature search of databases of available evidence in humans, with no language restriction, was conducted. Databases searched were MEDLINE (1946 to April 2017), EMBASE (1974 to April 2017) and the Cochrane Library (1999 to April 2017). A total of 57 records were included in the present review: 39 observational studies (25 prospective, 14 retrospective), 6 case reports/series and 12 conference abstracts. ARC has been reported to range from 14–80%. ARC is currently defined as an increased creatinine clearance of greater than 130 mL/min/1.73 m² best measured by 8–24 h urine collection. Patients exhibiting ARC tend to be younger (<50 years old), of male gender, had a recent history of trauma, and had lower critical illness severity scores. Numerous studies have reported antimicrobials treatment failures when using standard dosing regimens in patients with ARC. In conclusion, ARC is an important phenomenon that might have significant impact on outcome in critically ill patients. Identifying patients at risk, using higher doses of renally eliminated drugs or use of non-renally eliminated alternatives might need to be considered in ICU patients with ARC. More research is needed to solidify dosing recommendations of various drugs in patients with ARC. Full article

(This article belongs to the Special Issue Pharmacokinetics and Drug Metabolism in Canada: The Current Landscape)

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Open AccessArticle

Pharmacokinetic and Toxicodynamic Characterization of a Novel Doxorubicin Derivative

by Samaa Alrushaid, Casey L. Sayre, Jaime A. Yáñez, M. Laird Forrest, Sanjeewa N. Senadheera, Frank J. Burczynski, Raimar Löbenberg and Neal M. Davies

Pharmaceutics 2017, 9(3), 35; https://doi.org/10.3390/pharmaceutics9030035 - 13 Sep 2017

Cited by 28 | Viewed by 6986

Abstract

Doxorubicin (Dox) is an effective anti-cancer medication with poor oral bioavailability and systemic toxicities. DoxQ was developed by conjugating Dox to the lymphatically absorbed antioxidant quercetin to improve Dox’s bioavailability and tolerability. The purpose of this study was to characterize the pharmacokinetics and [...] Read more.

Doxorubicin (Dox) is an effective anti-cancer medication with poor oral bioavailability and systemic toxicities. DoxQ was developed by conjugating Dox to the lymphatically absorbed antioxidant quercetin to improve Dox’s bioavailability and tolerability. The purpose of this study was to characterize the pharmacokinetics and safety of Dox after intravenous (IV) and oral (PO) administration of DoxQ or Dox (10 mg/kg) and investigate the intestinal lymphatic delivery of Dox after PO DoxQ administration in male Sprague–Dawley rats. Drug concentrations in serum, urine, and lymph were quantified by HPLC with fluorescence detection. DoxQ intact IV showed a 5-fold increase in the area under the curve (AUC)—18.6 ± 1.98 compared to 3.97 ± 0.71 μg * h/mL after Dox—and a significant reduction in the volume of distribution (V_ss): 0.138 ± 0.015 versus 6.35 ± 1.06 L/kg. The fraction excreted unchanged in urine (f_e) of IV DoxQ and Dox was ~5% and ~11%, respectively. Cumulative amounts of Dox in the mesenteric lymph fluid after oral DoxQ were twice as high as Dox in a mesenteric lymph duct cannulation rat model. Oral DoxQ increased AUC of Dox by ~1.5-fold compared to after oral Dox. Concentrations of β-N-Acetylglucosaminidase (NAG) but not cardiac troponin (cTnI) were lower after IV DoxQ than Dox. DoxQ altered the pharmacokinetic disposition of Dox, improved its renal safety and oral bioavailability, and is in part transported through intestinal lymphatics. Full article

(This article belongs to the Special Issue Pharmacokinetics and Drug Metabolism in Canada: The Current Landscape)

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Open AccessArticle

Comparative Pharmacokinetic Study for Linezolid and Two Novel Antibacterial Oxazolidinone Derivatives in Rabbits: Can Differences in the Pharmacokinetic Properties Explain the Discrepancies between Their In Vivo and In Vitro Antibacterial Activities?

by Mohsen A. Hedaya, Vidhya Thomas, Mohamed E. Abdel-Hamid, Elijah O. Kehinde and Oludotun A. Phillips

Pharmaceutics 2017, 9(3), 34; https://doi.org/10.3390/pharmaceutics9030034 - 7 Sep 2017

Cited by 7 | Viewed by 5999

Abstract

This is a comparative pharmacokinetics study of linezolid (Lzd), and two novel oxazolidinone antibacterial agents—PH027 and PH051—in rabbits to determine if the discrepancy between the in vitro and in vivo activities of the novel compounds is due to pharmacokinetic factors. The pharmacokinetics after [...] Read more.

This is a comparative pharmacokinetics study of linezolid (Lzd), and two novel oxazolidinone antibacterial agents—PH027 and PH051—in rabbits to determine if the discrepancy between the in vitro and in vivo activities of the novel compounds is due to pharmacokinetic factors. The pharmacokinetics after IV and oral administration, plasma protein binding and tissue distribution for the three compounds were compared. The elimination half-lives were 52.4 ± 6.3, 68.7 ± 12.1 and 175 ± 46.1 min for Lzd, PH027 and PH051, respectively. The oral bioavailability for Lzd, PH027 and PH051 administered as suspension were 38.7%, 22.1% and 4.73%, which increased significantly when administered as microemulsion to 51.7%, 72.9% and 13.9%. The plasma protein binding were 32–34%, 37–38% and 90–91% for Lzd, PH027 and PH051. The tissue distribution for PH027 and PH051 in all investigated tissues were higher than that for Lzd. It can be concluded that the lower bioavailability of PH027 and PH051 compared to Lzd when administered as suspension is the main cause of their lower in vivo activity, despite their comparable in vitro activity. Differences in the other pharmacokinetic characteristics cannot explain the lower in vivo activity. The in vivo activity of the novel compounds should be re-evaluated using formulations with good oral bioavailability. Full article

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Open AccessReview

Transdermal Permeation of Drugs in Various Animal Species

by Hiroaki Todo

Pharmaceutics 2017, 9(3), 33; https://doi.org/10.3390/pharmaceutics9030033 - 6 Sep 2017

Cited by 158 | Viewed by 9899

Abstract

Excised human skin is utilized for in vitro permeation experiments to evaluate the safety and effect of topically-applied drugs by measuring its skin permeation and concentration. However, ethical considerations are the major problem for using human skin to evaluate percutaneous absorption. Moreover, large [...] Read more.

Excised human skin is utilized for in vitro permeation experiments to evaluate the safety and effect of topically-applied drugs by measuring its skin permeation and concentration. However, ethical considerations are the major problem for using human skin to evaluate percutaneous absorption. Moreover, large variations have been found among human skin specimens as a result of differences in age, race, and anatomical donor site. Animal skins are used to predict the in vivo human penetration/permeation of topically-applied chemicals. In the present review, skin characteristics, such as thickness of skin, lipid content, hair follicle density, and enzyme activity in each model are compared to human skin. In addition, intra- and inter-individual variation in animal models, permeation parameter correlation between animal models and human skin, and utilization of cultured human skin models are also descried. Pig, guinea pig, and hairless rat are generally selected for this purpose. Each animal model has advantages and weaknesses for utilization in in vitro skin permeation experiments. Understanding of skin permeation characteristics such as permeability coefficient (P), diffusivity (D), and partition coefficient (K) for each skin model would be necessary to obtain better correlations for animal models to human skin permeation. Full article

(This article belongs to the Special Issue Recent Technology of Transdermal and Topical Drug Delivery)

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Open AccessReview

Revisiting the Latency of Uridine Diphosphate-Glucuronosyltransferases (UGTs)—How Does the Endoplasmic Reticulum Membrane Influence Their Function?

by Yuejian Liu and Michael W. H. Coughtrie

Pharmaceutics 2017, 9(3), 32; https://doi.org/10.3390/pharmaceutics9030032 - 30 Aug 2017

Cited by 24 | Viewed by 10639

Abstract

Uridine diphosphate-glucuronosyltransferases (UGTs) are phase 2 conjugation enzymes mainly located in the endoplasmic reticulum (ER) of the liver and many other tissues, and can be recovered in artificial ER membrane preparations (microsomes). They catalyze glucuronidation reactions in various aglycone substrates, contributing significantly to [...] Read more.

Uridine diphosphate-glucuronosyltransferases (UGTs) are phase 2 conjugation enzymes mainly located in the endoplasmic reticulum (ER) of the liver and many other tissues, and can be recovered in artificial ER membrane preparations (microsomes). They catalyze glucuronidation reactions in various aglycone substrates, contributing significantly to the body’s chemical defense mechanism. There has been controversy over the last 50 years in the UGT field with respect to the explanation for the phenomenon of latency: full UGT activity revealed by chemical or physical disruption of the microsomal membrane. Because latency can lead to inaccurate measurements of UGT activity in vitro, and subsequent underprediction of drug clearance in vivo, it is important to understand the mechanisms behind this phenomenon. Three major hypotheses have been advanced to explain UGT latency: compartmentation, conformation, and adenine nucleotide inhibition. In this review, we discuss the evidence behind each hypothesis in depth, and suggest some additional studies that may reveal more information on this intriguing phenomenon. Full article

(This article belongs to the Special Issue Pharmacokinetics and Drug Metabolism in Canada: The Current Landscape)

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Open AccessArticle

Development and Evaluation of Topical Gabapentin Formulations

by Christopher J. Martin, Natalie Alcock, Sarah Hiom and James C. Birchall

Pharmaceutics 2017, 9(3), 31; https://doi.org/10.3390/pharmaceutics9030031 - 30 Aug 2017

Cited by 20 | Viewed by 12075

Abstract

Topical delivery of gabapentin is desirable to treat peripheral neuropathic pain conditions whilst avoiding systemic side effects. To date, reports of topical gabapentin delivery in vitro have been variable and dependent on the skin model employed, primarily involving rodent and porcine models. In [...] Read more.

Topical delivery of gabapentin is desirable to treat peripheral neuropathic pain conditions whilst avoiding systemic side effects. To date, reports of topical gabapentin delivery in vitro have been variable and dependent on the skin model employed, primarily involving rodent and porcine models. In this study a variety of topical gabapentin formulations were investigated, including Carbopol^® hydrogels containing various permeation enhancers, and a range of proprietary bases including a compounded Lipoderm^® formulation; furthermore microneedle facilitated delivery was used as a positive control. Critically, permeation of gabapentin across a human epidermal membrane in vitro was assessed using Franz-type diffusion cells. Subsequently this data was contextualised within the wider scope of the literature. Although reports of topical gabapentin delivery have been shown to vary, largely dependent upon the skin model used, this study demonstrated that 6% (w/w) gabapentin 0.75% (w/w) Carbopol^® hydrogels containing 5% (w/w) DMSO or 70% (w/w) ethanol and a compounded 10% (w/w) gabapentin Lipoderm^® formulation were able to facilitate permeation of the molecule across human skin. Further pre-clinical and clinical studies are required to investigate the topical delivery performance and pharmacodynamic actions of prospective formulations. Full article

(This article belongs to the Special Issue Penetration Enhancement of Topical Formulations)

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Open AccessArticle

Pharmacokinetic Analysis of an Oral Multicomponent Joint Dietary Supplement (Phycox^®) in Dogs

by Stephanie E. Martinez, Ryan Lillico, Ted M. Lakowski, Steven A. Martinez and Neal M. Davies

Pharmaceutics 2017, 9(3), 30; https://doi.org/10.3390/pharmaceutics9030030 - 18 Aug 2017

Cited by 7 | Viewed by 6941

Abstract

Despite the lack of safety, efficacy and pharmacokinetic (PK) studies, multicomponent dietary supplements (nutraceuticals) have become increasingly popular as primary or adjunct therapies for clinical osteoarthritis in veterinary medicine. Phycox^® is a line of multicomponent joint support supplements marketed for joint health [...] Read more.

Despite the lack of safety, efficacy and pharmacokinetic (PK) studies, multicomponent dietary supplements (nutraceuticals) have become increasingly popular as primary or adjunct therapies for clinical osteoarthritis in veterinary medicine. Phycox^® is a line of multicomponent joint support supplements marketed for joint health in dogs and horses. Many of the active constituents are recognized anti-inflammatory and antioxidant agents. Due to a lack of PK studies in the literature for the product, a pilot PK study of select constituents in Phycox^® was performed in healthy dogs. Two novel methods of analysis were developed and validated for quantification of glucosamine and select polyphenols using liquid chromatography-tandem mass spectrometry. After a single oral (PO) administrated dose of Phycox^®, a series of blood samples from dogs were collected for 24 h post-dose and analyzed for concentrations of glucosamine HCl, hesperetin, resveratrol and naringenin. Non-compartmental PK analyses were carried out. Glucosamine was detected up to 8 h post-dose with a T_max of 2 h and C_max of 9.69 μg/mL. The polyphenols were not found at detectable concentrations in serum samples. Co-administration of glucosamine in the Phycox^® formulation may enhance the absorption of glucosamine as determined by comparison of glucosamine PK data in the literature. Full article

(This article belongs to the Special Issue Pharmacokinetics and Drug Metabolism in Canada: The Current Landscape)

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Open AccessArticle

Efficient Transdermal Delivery of Alendronate, a Nitrogen-Containing Bisphosphonate, Using Tip-Loaded Self-Dissolving Microneedle Arrays for the Treatment of Osteoporosis

by Hidemasa Katsumi, Yutaro Tanaka, Kaori Hitomi, Shu Liu, Ying-shu Quan, Fumio Kamiyama, Toshiyasu Sakane and Akira Yamamoto

Pharmaceutics 2017, 9(3), 29; https://doi.org/10.3390/pharmaceutics9030029 - 17 Aug 2017

Cited by 36 | Viewed by 6977

Abstract

To improve the transdermal bioavailability and safety of alendronate (ALN), a nitrogen-containing bisphosphonate, we developed self-dissolving microneedle arrays (MNs), in which ALN is loaded only at the tip portion of micron-scale needles by a dip-coating method (ALN(TIP)–MN). We observed micron-scale pores in rat [...] Read more.

To improve the transdermal bioavailability and safety of alendronate (ALN), a nitrogen-containing bisphosphonate, we developed self-dissolving microneedle arrays (MNs), in which ALN is loaded only at the tip portion of micron-scale needles by a dip-coating method (ALN(TIP)–MN). We observed micron-scale pores in rat skin just after application of ALN(TIP)–MN, indicating that transdermal pathways for ALN were created by MN. ALN was rapidly released from the tip of MNs as observed in an in vitro release study. The tip portions of MNs completely dissolved in the rat skin within 5 min after application in vivo. After application of ALN(TIP)–MN in mice, the plasma concentration of ALN rapidly increased, and the bioavailability of ALN was approximately 96%. In addition, the decrease in growth plate was effectively suppressed by this efficient delivery of ALN in a rat model of osteoporosis. Furthermore, no skin irritation was observed after application of ALN(TIP)–MN and subcutaneous injection of ALN, while mild skin irritation was induced by whole-ALN-loaded MN (ALN–MN)—in which ALN is contained in the whole of the micron-scale needles fabricated from hyaluronic acid—and intradermal injection of ALN. These findings indicate that ALN(TIP)–MN is a promising transdermal formulation for the treatment of osteoporosis without skin irritation. Full article

(This article belongs to the Special Issue Recent Technology of Transdermal and Topical Drug Delivery)

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Open AccessArticle

Theophylline-7β-d-Ribofuranoside (Theonosine), a New Theophylline Metabolite Generated in Human and Animal Lung Tissue

by Daniel S. Sitar, James M. Bowen, Juan He, Angelo Tesoro and Michael Spino

Pharmaceutics 2017, 9(3), 28; https://doi.org/10.3390/pharmaceutics9030028 - 14 Aug 2017

Cited by 1 | Viewed by 6528

Abstract

While assessing the ability of mammalian lung tissue to metabolize theophylline, a new metabolite was isolated and characterized. The metabolite was produced by the microsomal fraction of lungs from several species, including rat, rabbit, dog, pig, sheep and human tissue. Metabolite production was [...] Read more.

While assessing the ability of mammalian lung tissue to metabolize theophylline, a new metabolite was isolated and characterized. The metabolite was produced by the microsomal fraction of lungs from several species, including rat, rabbit, dog, pig, sheep and human tissue. Metabolite production was blocked by boiling the microsomal tissue. This new metabolite, theophylline-7β-d-ribofuranoside (theonosine), was confirmed by several spectral methods and by comparison to an authentic synthetic compound. Tissue studies from rats, rabbits, dogs, and humans for cofactor involvement demonstrated an absolute requirement for NADP and enhanced metabolite production in the presence of magnesium ion. It remains to be demonstrated whether theonosine may contribute to the known pharmacological effects of theophylline. Full article

(This article belongs to the Special Issue Pharmacokinetics and Drug Metabolism in Canada: The Current Landscape)

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Open AccessArticle

Development of Novel Faster-Dissolving Microneedle Patches for Transcutaneous Vaccine Delivery

by Akihiko Ono, Sayami Ito, Shun Sakagami, Hideo Asada, Mio Saito, Ying-Shu Quan, Fumio Kamiyama, Sachiko Hirobe and Naoki Okada

Pharmaceutics 2017, 9(3), 27; https://doi.org/10.3390/pharmaceutics9030027 - 3 Aug 2017

Cited by 38 | Viewed by 10358 | Correction

Abstract

Microneedle (MN) patches are promising for transcutaneous vaccination because they enable vaccine antigens to physically penetrate the stratum corneum via low-invasive skin puncturing, and to be effectively delivered to antigen-presenting cells in the skin. In second-generation MN patches, the dissolving MNs release the [...] Read more.

Microneedle (MN) patches are promising for transcutaneous vaccination because they enable vaccine antigens to physically penetrate the stratum corneum via low-invasive skin puncturing, and to be effectively delivered to antigen-presenting cells in the skin. In second-generation MN patches, the dissolving MNs release the loaded vaccine antigen into the skin. To shorten skin application time for clinical practice, this study aims to develop novel faster-dissolving MNs. We designed two types of MNs made from a single thickening agent, carboxymethylcellulose (CMC) or hyaluronan (HN). Both CMC-MN and HN-MN completely dissolved in rat skin after a 5-min application. In pre-clinical studies, both MNs could demonstrably increase antigen-specific IgG levels after vaccination and prolong antigen deposition compared with conventional injections, and deliver antigens into resected human dermal tissue. In clinical research, we demonstrated that both MNs could reliably and safely puncture human skin without any significant skin irritation from transepidermal water loss measurements and ICDRG (International Contact Dermatitis Research Group) evaluation results. Full article

(This article belongs to the Special Issue Recent Technology of Transdermal and Topical Drug Delivery)

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Open AccessFeature PaperArticle

A Possible Percutaneous Penetration Pathway That Should Be Considered

by Ichiro Hatta, Noboru Ohta and Hiromitsu Nakazawa

Pharmaceutics 2017, 9(3), 26; https://doi.org/10.3390/pharmaceutics9030026 - 27 Jul 2017

Cited by 7 | Viewed by 4023

Abstract

The intercellular lipids in the stratum corneum form structures composed of ordered phases with orthorhombic and hexagonal hydrocarbon-chain packing structures and, in addition, a structure composed of a disordered fluid phase. Although the fluid phase plays an important role in percutaneous penetration, little [...] Read more.

The intercellular lipids in the stratum corneum form structures composed of ordered phases with orthorhombic and hexagonal hydrocarbon-chain packing structures and, in addition, a structure composed of a disordered fluid phase. Although the fluid phase plays an important role in percutaneous penetration, little attention has been paid to it in the literature thus far. Recently, a method to estimate the proportion of the fluid phase within the lipids of the stratum corneum was proposed and it was shown to reach about 80%. However, since that study assumed uniform extraction of the intercellular lipids from the stratum corneum, the analysis might give rise to an overestimation of the proportion of the lipids in the fluid phase. We developed a way to investigate the proportion of the lipids in the fluid phase by treating with ethanol, into which the lipids in the fluid phase might be dominantly dissolved. From the experiment we pointed out the possibility that the proportion of the lipids in the fluid phase reached more than 50% of the whole intercellular lipids. Therefore, the fluid-phase region in the intercellular lipid matrix should be taken into account when considering the percutaneous penetration mechanism. Full article

(This article belongs to the Special Issue Recent Technology of Transdermal and Topical Drug Delivery)

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Open AccessArticle

Veterinary Pharmaceutics: An Opportunity for Interprofessional Education in New Zealand?

by Arlene McDowell, Rebekah Beard, Anna Brightmore, Lisa W. Lu, Amelia McKay, Maadhuri Mistry, Kate Owen, Emma Swan and Jessica Young

Pharmaceutics 2017, 9(3), 25; https://doi.org/10.3390/pharmaceutics9030025 - 26 Jul 2017

Cited by 6 | Viewed by 4613

Abstract

Globally pharmacists are becoming increasingly involved in veterinary medicine; however, little is known about the level of interest for pharmacists playing a larger role in animal treatment in New Zealand. A key stakeholder in any progression of pharmacists becoming more involved in the [...] Read more.

Globally pharmacists are becoming increasingly involved in veterinary medicine; however, little is known about the level of interest for pharmacists playing a larger role in animal treatment in New Zealand. A key stakeholder in any progression of pharmacists becoming more involved in the practice of veterinary pharmacy is the veterinary profession. The aim of this study was to investigate views of veterinarians and veterinary students on the role of pharmacists supporting veterinarians with advice on animal medicines. Open interviews were conducted with veterinarians in Dunedin, New Zealand. Veterinary students at Massey University completed an online survey. Most veterinarians do not have regular communication with pharmacists regarding animal care, but believe it may be beneficial. In order to support veterinarians, pharmacists would need further education in veterinary medicine. Veterinary students believe there is opportunity for collaboration between professions provided that pharmacists have a better working knowledge of animal treatment. Most of the veterinary students surveyed perceive a gap in their knowledge concerning animal medicines, specifically pharmacology and compounding. While there is support for pharmacists contributing to veterinary medicine, particularly in the area of pharmaceutics, this is currently limited in New Zealand due to a lack of specialized education opportunities. Full article

(This article belongs to the Special Issue Veterinary Medicine)

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Open AccessArticle

Multiple Functions of D-α-Tocopherol Polyethylene Glycol 1000 Succinate (TPGS) as Curcumin Nanoparticle Stabilizer: In Vivo Kinetic Profile and Anti-Ulcerative Colitis Analysis in Animal Model

by Heni Rachmawati, Aditya Trias Pradana, Dewi Safitri and I Ketut Adnyana

Pharmaceutics 2017, 9(3), 24; https://doi.org/10.3390/pharmaceutics9030024 - 21 Jul 2017

Cited by 29 | Viewed by 6101

Abstract

This study was conducted to evaluate the potential benefit of particle reduction down to nanoscale on curcumin, a unique natural active compound facing therapeutic problems due to low solubility and permeability. In addition, the presence of TPGS as a surfactant for multiple functions [...] Read more.

This study was conducted to evaluate the potential benefit of particle reduction down to nanoscale on curcumin, a unique natural active compound facing therapeutic problems due to low solubility and permeability. In addition, the presence of TPGS as a surfactant for multiple functions on curcumin nanoparticle was addressed. Observation was focused on bioavailability enhancement after oral administration and local anti-inflammatory improvement after rectal dosing. Nanonization of curcumin was performed using an up-scalable top down method. Specific animal models were used to study the in vivo kinetic profile and the biological activity of curcumin nanoparticle, compared with curcumin powder. d-α-tocopherol polyethylene glycol 1000 succinate (TPGS)-stabilized curcumin nanoparticle was prepared through homogenization with high pressure of the 1500 bar. An in vivo study was performed after oral administration of the preparations to male healthy Wistar rats, to monitor the plasma kinetic profile of curcumin. The biological activity study was conducted after rectal administration of the preparations in Wistar rats induced by 2,4,6-trinitrobenzene sulfonic acid to develop ulcerative colitis. The curcumin nanoparticle with a size of approximately 200 nm was successfully produced and revealed a better in vivo kinetic profile over the larger size of curcumin mixed with TPGS, with bioavailability (AUC_0-∞) that was accounted for seven-fold. In addition, the TPGS-stabilized curcumin nanoparticle demonstrated a superior local anti-inflammatory effect in ulcerative colitis, indicated by the shifting of observed parameters close to the healthy status. The tremendously improved anti-inflammatory effect of the TPGS-stabilized curcumin nanoparticle was found with a very low dose. Reducing the particle size of curcumin down to ~200 nm with the presence of TPGS seems to be a promising approach to improving the therapeutic value of curcumin. Full article

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Open AccessArticle

Effect of Polymers on the Physicochemical Properties and Biological Performance of Fenoprofen Calcium Dihydrate-Triacetyl-β-Cyclodextrin Complex

by Hussein O. Ammar, Tarek S. Makram and Shaimaa Mosallam

Pharmaceutics 2017, 9(3), 23; https://doi.org/10.3390/pharmaceutics9030023 - 3 Jul 2017

Cited by 10 | Viewed by 5168

Abstract

Background: Fenoprofen calcium dehydrate (FCD) is counted as a non-steroidal, anti-inflammatory, anti-arthritic drug. FCD is slightly water soluble. It is indicated for mild pain relief, where the suggested dosage is 200 mg orally every 4 to 6 h. Aim: Reduce dissolution efficiency, reach [...] Read more.

Background: Fenoprofen calcium dehydrate (FCD) is counted as a non-steroidal, anti-inflammatory, anti-arthritic drug. FCD is slightly water soluble. It is indicated for mild pain relief, where the suggested dosage is 200 mg orally every 4 to 6 h. Aim: Reduce dissolution efficiency, reach an extended therapeutic effect and reduce the frequency of the drug side effects. Method: Combination of the co-evaporated drug:triacetyl-β-cyclodextrin complex prepared in a ratio of 1:3 and either of two polymers—hydroxylpropylmethyl cellulose (HPMC) or ethyl cellulose (EC)—in the same formulation. In vitro dissolution studies were carried in simulated gastric (pH 1.2) and intestinal (pH 6.8) fluids, by using the USP dissolution tester (rotating paddle apparatus). The FCD in vitro release from EC/drug complex was markedly retarded. Interaction between fenoprofen, TA-β-CD, EC, HPMC in the solid state were confirmed by FT-IR, DSC, XRD and SEM. In vivo studies assessed the anti-inflammatory and analgesic activities and the results were compared with the market product Nalfosab^® Capsules. Results: Remarkable inhibition of inflammation and nociception after 24 h was attained for EC/drug complex. Conclusions: EC/drug complex has a sustained effect due to high remaining amount after elapsing with remarkable inhibition of inflammation. Full article

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Open AccessArticle

Development and Characterization of an Amorphous Solid Dispersion of Furosemide in the Form of a Sublingual Bioadhesive Film to Enhance Bioavailability

by Viviana De Caro, Alessia Ajovalasit, Flavia Maria Sutera, Denise Murgia, Maria Antonietta Sabatino and Clelia Dispenza

Pharmaceutics 2017, 9(3), 22; https://doi.org/10.3390/pharmaceutics9030022 - 24 Jun 2017

Cited by 19 | Viewed by 6063

Abstract

Administered by an oral route, Furosemide (FUR), a diuretic used in several edematous states and hypertension, presents bioavailability problems, reported as a consequence of an erratic gastrointestinal absorption due to various existing polymorphic forms and low and pH-dependent solubility. A mucoadhesive sublingual fast-dissolving [...] Read more.

Administered by an oral route, Furosemide (FUR), a diuretic used in several edematous states and hypertension, presents bioavailability problems, reported as a consequence of an erratic gastrointestinal absorption due to various existing polymorphic forms and low and pH-dependent solubility. A mucoadhesive sublingual fast-dissolving FUR based film has been developed and evaluated in order to optimize the bioavailability of FUR by increasing solubility and guaranteeing a good dissolution reproducibility. The Differential Scanning Calorimetry (DSC) analyses confirmed that the film prepared using the solvent casting method entrapped FUR in the amorphous state. As a solid dispersion, FUR increases its solubility up to 28.36 mg/mL. Drug content, thickness, and weight uniformity of film were also evaluated. The measured Young’s Modulus, yield strength, and relative elongation of break percentage (EB%) allowed for the classification of the drug-loaded film as an elastomer. Mucoadhesive strength tests showed that the force to detach film from mucosa grew exponentially with increasing contact time up to 7667 N/m². FUR was quickly discharged from the film following a trend well fitted with the Weibull kinetic model. When applied on sublingual mucosa, the new formulation produced a massive drug flux in the systemic compartment. Overall, the proposed sublingual film enhances drug solubility and absorption, allowing for the prediction of a rapid onset of action and reproducible bioavailability in its clinical application. Full article

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Pharmaceutics, Volume 9, Issue 3 (September 2017) – 15 articles

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