Pharmaceutics

9 pages, 151 KiB

Open AccessArticle

Development and Validation of a Successful Microbiological Agar Assay for Determination of Ceftriaxone Sodium in Powder for Injectable Solution

by Patrícia V. Aléssio and Hérida R. N. Salgado^*

Post graduate Progam in Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Univ Estadual Paulista, Rod. Araraquara-Jaú, km 1, CEP 14801-902, Araraquara, SP, Brazil

Pharmaceutics 2012, 4(3), 334-342; https://doi.org/10.3390/pharmaceutics4030334 - 29 Jun 2012

Cited by 14 | Viewed by 8777

Abstract

Ceftriaxone sodium is a cephalosporin with broad-spectrum antimicrobial activity and belongs to the third generation of cephalosporins. Regarding the quality control of medicines, a validated microbiological assay for the determination of ceftriaxone sodium in powder for injectable solution has not been reported yet. [...] Read more.

Ceftriaxone sodium is a cephalosporin with broad-spectrum antimicrobial activity and belongs to the third generation of cephalosporins. Regarding the quality control of medicines, a validated microbiological assay for the determination of ceftriaxone sodium in powder for injectable solution has not been reported yet. This paper reports the development and validation of a simple, accurate and reproducible agar diffusion method to quantify ceftriaxone sodium in powder for injectable solution. The assay is based on the inhibitory effect of ceftriaxone sodium on the strain of Bacillus subtilis ATCC 9371 IAL 1027 used as test microorganism. The results were treated statistically by analysis of variance and were found to be linear (r = 0.999) in the selected range of 15.0–60.0 μg/mL, precise with a relative standard deviation (RSD) of repeatability intraday = 1.40%, accurate (100.46%) and robust with a RSD lower than 1.28%. The results demonstrated the validity of the proposed bioassay, which allows reliable ceftriaxone sodium quantitation in pharmaceutical samples and therefore can be used as a useful alternative methodology for the routine quality control of this medicine. Full article

▼ Show Figures

Figure 1

11 pages, 266 KiB

Open AccessArticle

Design of Skin Penetration Enhancers Using Replacement Methods for the Selection of the Molecular Descriptors

by Laurent Simon^* and Beshoy Abdelmalek

Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark NJ 07102, USA

Pharmaceutics 2012, 4(3), 343-353; https://doi.org/10.3390/pharmaceutics4030343 - 11 Jul 2012

Cited by 3 | Viewed by 7205

Abstract

Transdermal delivery of certain drugs is challenging because of skin barrier resistance. This study focuses on the implementation of feature-selection algorithms to design chemical penetration enhancers. A database, consisting of 145 polar and nonpolar chemicals, was chosen for the investigation. Replacement, enhanced replacement [...] Read more.

Transdermal delivery of certain drugs is challenging because of skin barrier resistance. This study focuses on the implementation of feature-selection algorithms to design chemical penetration enhancers. A database, consisting of 145 polar and nonpolar chemicals, was chosen for the investigation. Replacement, enhanced replacement and stepwise algorithms were applied to identify relevant structural properties of these compounds. The descriptors were calculated using Molecular Modeling Pro™ Plus. Based on the coefficient of determination, the replacement methods outperformed the stepwise approach in selecting the features that best correlated with the flux enhancement ratio. An artificial neural network model was built to map a subset of descriptors from sixty-one nonpolar enhancers onto the output vector. The R² value improved from 0.68, for a linear model, to 0.74, which shows that the improved framework might be effective in the design of compounds with user-defined properties. Full article

▼ Show Figures

Figure 1

12 pages, 236 KiB

Open AccessArticle

Application and Characterization of Gum from Bombax buonopozense Calyxes as an Excipient in Tablet Formulation

by Ndidi C. Ngwuluka^1,*, Jehu Kyari¹, John Taplong¹ and Onyinye J. Uwaezuoke²

¹ Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, University of Jos, Jos, 930001, Nigeria

² Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Olabisi Onabanjo University, Ago-Iwoye, 120005, Nigeria

Pharmaceutics 2012, 4(3), 354-365; https://doi.org/10.3390/pharmaceutics4030354 - 3 Aug 2012

Cited by 8 | Viewed by 7169

Abstract

This study was undertaken to explore gum from Bombax buonopozense calyxes as a binding agent in formulation of immediate release dosage forms using wet granulation method. The granules were characterized to assess the flow and compression properties and when compressed, non-compendial and compendial [...] Read more.

This study was undertaken to explore gum from Bombax buonopozense calyxes as a binding agent in formulation of immediate release dosage forms using wet granulation method. The granules were characterized to assess the flow and compression properties and when compressed, non-compendial and compendial tests were undertaken to assess the tablet properties for tablets prepared with bombax gum in comparison with those prepared with tragacanth and acacia gums. Granules prepared with bombax exhibited good flow and compressible properties with angle of repose 28.60°, Carr’s compressibility of 21.30% and Hausner’s quotient of 1.27. The tablets were hard, but did not disintegrate after one hour. Furthermore, only 52.5% of paracetamol was released after one hour. The drug release profile followed zero order kinetics. Tablets prepared with bombax gum have the potential to deliver drugs in a controlled manner over a prolonged period at a constant rate. Full article

(This article belongs to the Special Issue Oral and Buccal Drug Delivery)

▼ Show Figures

Graphical abstract

11 pages, 218 KiB

Open AccessArticle

Using Ion-Selective Electrodes to Study the Drug Release from Porous Cellulose Matrices

by Hossein Vakili^1,*, Natalja Genina¹, Henrik Ehlers¹, Johan Bobacka² and Niklas Sandler¹

¹ Pharmaceutical Sciences Laboratory, Department of Biosciences, Abo Akademi University Artillerigatan 6 A, 20520, Turku, Finland

² Analytical Chemistry Laboratory, Department of Chemical Engineering, Biskopsgatan 8, 20500, Turku, Finland

Pharmaceutics 2012, 4(3), 366-376; https://doi.org/10.3390/pharmaceutics4030366 - 7 Aug 2012

Cited by 13 | Viewed by 6699

Abstract

Polyvinyl chloride (PVC)-based solid-contact ion-selective electrodes (SC-ISEs), responding to propranolol hydrochloride (Pr⁺) and lidocaine hydrochloride (Ld⁺) cations as the model drugs with potassium tetrakis(4-chlorophenyl) borate (KTpClPB) as the ion exchanger, were studied. Different drug-polymer solutions were prepared with the [...] Read more.

Polyvinyl chloride (PVC)-based solid-contact ion-selective electrodes (SC-ISEs), responding to propranolol hydrochloride (Pr⁺) and lidocaine hydrochloride (Ld⁺) cations as the model drugs with potassium tetrakis(4-chlorophenyl) borate (KTpClPB) as the ion exchanger, were studied. Different drug-polymer solutions were prepared with the model drugs, using different blend ratios of ethylcellulose (EC) and hydroxypropyl cellulose (HPC). Two different solid dosage forms were used. Polymer films were produced by solvent casting method and drug containing porous cellulose samples were prepared by depositing the drug-polymer solutions onto filter paper substrates. The quality of the electrodes and the release profile of Pr⁺ and Ld⁺ were investigated with the potentiometric method. The results were compared to UV spectrophotometry. The electrodes were found to be sensitive, precise and functional with a Nernstian behavior over the range of 1.0 × 10⁻³–3.1 × 10⁻⁶ M (9.2 × 10⁻⁴–3.0 × 10⁻¹ mg/mL) and 1 × 10⁻³–2 × 10⁻⁶ M (5.4 × 10⁻⁴–2.7 × 10⁻¹ mg/mL) at 25 °C for Pr⁺ and Ld⁺ sensitive electrodes, respectively. The dynamic response time for the electrodes was less than 10 s. The Pr⁺ release from porous filter paper was always higher than its equivalent film formulation. Also, lidocaine had higher and faster release from the samples with higher drug concentration. The comparison of the two analytical methods showed near identical results. The ISEs provided a powerful and flexible alternative to UV method in determination of drug release from porous cellulose substrates in a small scale dissolution testing. Full article

▼ Show Figures

Graphical abstract

8 pages, 161 KiB

Open AccessArticle

The Effect of Diluted Penetration Enhancer in Nebulized Mist versus Liquid Drop Preparation Forms on Retrobulbar Blood Flow in Healthy Human Subjects

by Sally Primus¹, Ingrida Januleviciene², Brent Siesky¹, Austin Gerber¹, Patrick Egan¹, Annahita Amireskandari¹, Lina Siaudvytyte², Ruta Barsauskaite² and Alon Harris^1,*

¹ Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA

² Department of Ophthalmology, Hospital of Lithuanian University of Health Sciences Kaunas Clinics, LT-50009 Kaunas, Lithuania

Pharmaceutics 2012, 4(3), 377-384; https://doi.org/10.3390/pharmaceutics4030377 - 8 Aug 2012

Cited by 1 | Viewed by 6212

Abstract

The aim of this study was to compare the effects of nebulized mist and liquid drop applications on retrobulbar blood flow. A prospective, non-randomized clinical trial was used to collect data from 40 healthy human eyes. Color Doppler Imaging determined peak systolic (PSV) [...] Read more.

The aim of this study was to compare the effects of nebulized mist and liquid drop applications on retrobulbar blood flow. A prospective, non-randomized clinical trial was used to collect data from 40 healthy human eyes. Color Doppler Imaging determined peak systolic (PSV) and end diastolic (EDV) blood flow velocities and resistance index (RI) in the ophthalmic artery after both applications. Measurements were taken at baseline and at 1 min post-treatment in both eyes with 5 min measurements in the treatment eye only. p values ≤ 0.05 were considered statistically significant. Mist application to treatment eye produced an increase in 1 min and 5 min PSV and EDV (0.001 < p < 0.03) and a decrease in 5 min RI (p = 0.01), with no significant changes in PSV, EDV or RI of control eye or in treatment eye 1 min RI (p > 0.05). Drop application to treatment eye produced an increase in PSV (p < 0.001) and EDV (p = 0.01) at 1 min, with an increase in control eye 1 min PSV and EDV (p = 0.03). There were no statistically significant changes in treatment eye PSV, EDV and RI after 5 min (p > 0.05). The use of nebulized mist may provide an effective alternative to liquid drop medication application. Full article

28 pages, 5745 KiB

Open AccessArticle

Levofloxacin-Proliposomes: Opportunities for Use in Lung Tuberculosis

by Wipaporn Rojanarat^1,2, Titpawan Nakpheng², Ekawat Thawithong², Niracha Yanyium³ and Teerapol Srichana^1,2,*

¹ Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand

² Drug Delivery System Excellence Center, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand

³ Department of Pharmacology, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand

Pharmaceutics 2012, 4(3), 385-412; https://doi.org/10.3390/pharmaceutics4030385 - 13 Aug 2012

Cited by 59 | Viewed by 9442

Abstract

Levofloxacin (LEV) is a relatively new-generation fluoroquinolone antibiotic that has good activity against Mycobacterium tuberculosis. The aims of this study were to develop and evaluate LEV-proliposomes in a dry powder aerosol form for pulmonary delivery. LEV-proliposomes containing LEV, soybean phosphatidylcholine, cholesterol and [...] Read more.

Levofloxacin (LEV) is a relatively new-generation fluoroquinolone antibiotic that has good activity against Mycobacterium tuberculosis. The aims of this study were to develop and evaluate LEV-proliposomes in a dry powder aerosol form for pulmonary delivery. LEV-proliposomes containing LEV, soybean phosphatidylcholine, cholesterol and porous mannitol were prepared by a spray drying technique. The physicochemical properties of LEV-proliposomes were determined using a cascade impactor, X-ray diffraction (XRD), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). The toxicity of proliposomes to respiratory-associated cell lines and its potential to provoke immunological responses from alveolar macrophages (AMs) were evaluated. Antimycobacterial activity using flow cytometry and an in vivo repeated dose toxicity test in rats were carried out. LEV-proliposomes were successfully prepared with mass median aerodynamic diameters of 4.15–4.44 μm and with fine particle fractions (aerosolized particles of less than 4.4 µm) of 13%–38% at 60 L/min. LEV-proliposomes were less toxic to respiratory-associated cells than LEV, and did not activate AMs to produce inflammatory mediators that included interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and nitric oxide. The minimum inhibitory concentration (MIC) against M. bovis of LEV and LEV-proliposomes containing LEV 10% were 1 and 0.5 µg/mL, respectively. The efficacy of LEV-proliposomes against M. bovis was significantly higher than that of free LEV (p < 0.05). The efficacy of the LEV-proliposomes against M. tuberculosis was equal to that of the free LEV (MIC = 0.195 µg/mL). In a repeated dose toxicity study in rats, renal and liver toxicity was not observed. LEV-proliposomes should now be tested as an alternative formulation for delivering LEV to the lower airways. Full article

▼ Show Figures

Figure 1

17 pages, 211 KiB

Open AccessArticle

Diclofenac Salts, VIII. Effect of the Counterions on the Permeation through Porcine Membrane from Aqueous Saturated Solutions

by Adamo Fini^1,*, Glenda Bassini¹, Annamaria Monastero¹ and Cristina Cavallari²

¹ Department SMETEC, University of Bologna, Via San Donato 15, 40127 Bologna, Italy

² Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro 6, 40127 Bologna, Italy

Pharmaceutics 2012, 4(3), 413-429; https://doi.org/10.3390/pharmaceutics4030413 - 12 Sep 2012

Cited by 46 | Viewed by 14345

Abstract

The following bases: monoethylamine (EtA), diethylamine (DEtA), triethylamine (TEtA), monoethanolamine (MEA), diethanolamine (DEA), triethanolamine (TEA), pyrrolidine (Py), piperidine (Pp), morpholine (M), piperazine (Pz) and their N-2-hydroxyethyl (HE) analogs were employed to prepare 14 diclofenac salts. The salts were re-crystallized from water in [...] Read more.

The following bases: monoethylamine (EtA), diethylamine (DEtA), triethylamine (TEtA), monoethanolamine (MEA), diethanolamine (DEA), triethanolamine (TEA), pyrrolidine (Py), piperidine (Pp), morpholine (M), piperazine (Pz) and their N-2-hydroxyethyl (HE) analogs were employed to prepare 14 diclofenac salts. The salts were re-crystallized from water in order to obtain forms that are stable in the presence of water. Vertical Franz-type cells with a diffusional surface area of 9.62 cm² were used to study the permeation of these diclofenac salts from their saturated solutions through an internal pig ear membrane. The receptor compartments of the cells contained 100 mL of phosphate buffer (pH 7.4); a saturated solution (5 mL) of each salt was placed in the donor compartment, thermostated at 37 °C. Aliquots were withdrawn at predetermined time intervals over 8 h and then immediately analyzed by HPLC. Fluxes were determined by plotting the permeated amount, normalized for the membrane surface area versus time. Permeation coefficients were obtained dividing the flux values J by the concentration of the releasing phase—that is, water solubility of each salt. Experimental results show that fluxes could be measured when diclofenac salts with aliphatic amines are released from a saturated aqueous solution. Different chemical species (acid, anion, ion pairs) contribute to permeation of the anti-inflammatory agent even though ion-pairs could be hypothesized to operate to a greater extent. Permeation coefficients were found higher when the counterion contains a ring; while hydroxy groups alone do not appear to play an important role, the ring could sustain permeation, disrupting the organized domains of the membrane. Full article

▼ Show Figures

Figure 1

12 pages, 590 KiB

Open AccessArticle

Influence of the Efavirenz Micronization on Tableting and Dissolution

by Eduardo Costa Pinto¹, Flávia Almada do Carmo^1,*, Thiago da Silva Honório¹, Rita de Cássia da Silva Ascenção Barros¹, Helena Carla Rangel Castro², Carlos Rangel Rodrigues¹, Valéria Sant'Anna Dantas Esteves^1,3, Helvécio Vinícius Antunes Rocha³, Valeria Pereira de Sousa¹ and Lucio Mendes Cabral¹

² Laboratory of Antibiotics, Biochemistry, Institute of Biology, Universidade Federal Fluminense, Campus of Valonguinho, Niterói, RJ, CEP: 24.210-130, Brazil

³ Institute of Drug Technology, Fundação Oswaldo Cruz, Av. Comandante Guaranys, 447, Curicica, Rio de Janeiro, RJ, CEP: 22.775-903, Brazil

Pharmaceutics 2012, 4(3), 430-441; https://doi.org/10.3390/pharmaceutics4030430 - 12 Sep 2012

Cited by 12 | Viewed by 8383

Abstract

The purpose of this study was to propose an analytical procedure that provides the effects of particle size and surface area on dissolution of efavirenz. Five different batches obtained by different micronization processes and with different particle size distribution and surface area were [...] Read more.

The purpose of this study was to propose an analytical procedure that provides the effects of particle size and surface area on dissolution of efavirenz. Five different batches obtained by different micronization processes and with different particle size distribution and surface area were studied. The preformulation studies and dissolution curves were used to confirm the particle size distribution effect on drug solubility. No polymorphic variety or amorphization was observed in the tested batches and the particle size distribution was determined as directly responsible for the improvement of drug dissolution. The influence of the preparation process on the tablets derived from efavirenz was observed in the final dissolution result in which agglomeration, usually seen in non-lipophilic micronized material, was avoided through the use of an appropriate wet granulation method. For these reasons, micronization may represent one viable alternative for the formulation of brick dust drugs. Full article

▼ Show Figures

Figure 1

37 pages, 537 KiB

Open AccessReview

Practical Dynamic Contrast Enhanced MRI in Small Animal Models of Cancer: Data Acquisition, Data Analysis, and Interpretation

by Stephanie L. Barnes^1,2, Jennifer G. Whisenant^1,3, Mary E. Loveless¹ and Thomas E. Yankeelov^{1,2,3,4,5,6,7,*}

¹ Institute of Imaging Science, Vanderbilt University, Nashville, TN, 37232-2310, USA

² Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN 37232, USA

³ Program in Chemical and Physical Biology, Vanderbilt University, Nashville, TN 37232, USA

⁴ Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235-1826, USA

⁵ Department of Physics and Astronomy, Vanderbilt University, Nashville, TN 37235, USA

⁶ Department of Cancer Biology, Vanderbilt University, Nashville, TN 37232-6838, USA

⁷ Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN 37232, USA

Pharmaceutics 2012, 4(3), 442-478; https://doi.org/10.3390/pharmaceutics4030442 - 19 Sep 2012

Cited by 75 | Viewed by 16493

Abstract

Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) consists of the continuous acquisition of images before, during, and after the injection of a contrast agent. DCE-MRI allows for noninvasive evaluation of tumor parameters related to vascular perfusion and permeability and tissue volume fractions, and [...] Read more.

Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) consists of the continuous acquisition of images before, during, and after the injection of a contrast agent. DCE-MRI allows for noninvasive evaluation of tumor parameters related to vascular perfusion and permeability and tissue volume fractions, and is frequently employed in both preclinical and clinical investigations. However, the experimental and analytical subtleties of the technique are not frequently discussed in the literature, nor are its relationships to other commonly used quantitative imaging techniques. This review aims to provide practical information on the development, implementation, and validation of a DCE-MRI study in the context of a preclinical study (though we do frequently refer to clinical studies that are related to these topics). Full article

(This article belongs to the Special Issue DCE-MRI in Preclinical Imaging)

▼ Show Figures

Figure 1

Journal Menu

Journal Browser

Pharmaceutics, Volume 4, Issue 3 (September 2012) – 10 articles , Pages 334-493

Further Information

Guidelines

MDPI Initiatives

Follow MDPI