Pharmaceutics

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248 KiB

Open AccessArticle

Optimization of Salbutamol Sulfate Dissolution from Sustained Release Matrix Formulations Using an Artificial Neural Network

by Faith Chaibva, Michael Burton and Roderick B. Walker

Pharmaceutics 2010, 2(2), 182-198; https://doi.org/10.3390/pharmaceutics2020182 - 6 May 2010

Cited by 34 | Viewed by 11500

Abstract

An artificial neural network was used to optimize the release of salbutamol sulfate from hydrophilic matrix formulations. Model formulations to be used for training, testing and validating the neural network were manufactured with the aid of a central composite design with varying the [...] Read more.

An artificial neural network was used to optimize the release of salbutamol sulfate from hydrophilic matrix formulations. Model formulations to be used for training, testing and validating the neural network were manufactured with the aid of a central composite design with varying the levels of Methocel^® K100M, xanthan gum, Carbopol^® 974P and Surelease^® as the input factors. In vitro dissolution time profiles at six different sampling times were used as target data in training the neural network for formulation optimization. A multi layer perceptron with one hidden layer was constructed using Matlab^®, and the number of nodes in the hidden layer was optimized by trial and error to develop a model with the best predictive ability. The results revealed that a neural network with nine nodes was optimal for developing and optimizing formulations. Simulations undertaken with the training data revealed that the constructed model was useable. The optimized neural network was used for optimization of formulation with desirable release characteristics and the results indicated that there was agreement between the predicted formulation and the manufactured formulation. This work illustrates the possible utility of artificial neural networks for the optimization of pharmaceutical formulations with desirable performance characteristics. Full article

(This article belongs to the Special Issue What's on Board in Pharmaceutics)

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165 KiB

Open AccessArticle

Strategies for Developing Sensitive and Automated LC-MS/MS Assays of a Pharmaceutical Compound and Its Metabolite from Whole Blood Matrix

by Raymond N. Xu, Jill Polzin, Michelle Kranz, Phillip Vaca, Maria Metchkarova, Matthew J. Rieser and Tawakol A. El-Shourbagy

Pharmaceutics 2010, 2(2), 159-170; https://doi.org/10.3390/pharmaceutics2020159 - 30 Apr 2010

Cited by 2 | Viewed by 8256

Abstract

When compared with biological samples in other matrices (plasma, urine, etc.) that are typically seen in bioanalytical applications, whole blood samples present unique challenges in method development, because of the viscous nature of blood and complexity of its constituents. In this article, [...] Read more.

When compared with biological samples in other matrices (plasma, urine, etc.) that are typically seen in bioanalytical applications, whole blood samples present unique challenges in method development, because of the viscous nature of blood and complexity of its constituents. In this article, we have developed and validated a series of quantitative bioanalytical methods for the determination of a pharmaceutical compound, Compound A, and its phosphate metabolite from whole blood matrices using liquid chromatography tandem mass spectrometry. All methods employed a simple protein precipitation procedure that was automated in 96-well format. The methods were subjected to vigorous tests in precision, accuracy, matrix effect, reproducibility, and robustness. Monolithic chromatography was used to improve sample throughput in one of the methods. The results also demonstrated that proper sample preparation procedures, such as sample transfer and lysing of blood cells prior to the extraction, are key to reproducible results for pharmacokinetic parameter determination. Full article

(This article belongs to the Special Issue What's on Board in Pharmaceutics)

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625 KiB

Open AccessArticle

Diclofenac Salts. V. Examples of Polymorphism among Diclofenac Salts with Alkyl-hydroxy Amines Studied by DSC and HSM

by Adamo Fini, Cristina Cavallari and Francesca Ospitali

Pharmaceutics 2010, 2(2), 136-158; https://doi.org/10.3390/pharmaceutics2020136 - 27 Apr 2010

Cited by 23 | Viewed by 11663

Abstract

Nine diclofenac salts prepared with alkyl-hydroxy amines were analyzed for their properties to form polymorphs by DSC and HSM techniques. Thermograms of the forms prepared from water or acetone are different in most cases, suggesting frequent examples of polymorphism among these salts. Polymorph [...] Read more.

Nine diclofenac salts prepared with alkyl-hydroxy amines were analyzed for their properties to form polymorphs by DSC and HSM techniques. Thermograms of the forms prepared from water or acetone are different in most cases, suggesting frequent examples of polymorphism among these salts. Polymorph transition can be better highlighted when analysis is carried out by thermo-microscopy, which in most cases made it possible to observe the processes of melting of the metastable form and re-crystallization of the stable one. Solubility values were qualitatively related to the crystal structure of the salts and the molecular structure of the cation. Full article

(This article belongs to the Special Issue What's on Board in Pharmaceutics)

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4875 KiB

Open AccessArticle

Transcellular Transport of Heparin-coated Magnetic Iron Oxide Nanoparticles (Hep-MION) Under the Influence of an Applied Magnetic Field

by Kyoung Ah Min, Faquan Yu, Victor C. Yang, Xinyuan Zhang and Gus R. Rosania

Pharmaceutics 2010, 2(2), 119-135; https://doi.org/10.3390/pharmaceutics2020119 - 26 Apr 2010

Cited by 18 | Viewed by 10383

Abstract

In this study, magnetic iron oxide nanoparticles coated with heparin (Hep-MION) were synthesized and the transcellular transport of the nanoparticles across epithelial cell monolayers on porous polyester membranes was investigated. An externally applied magnetic field facilitated the transport of the Hep-MION across cell [...] Read more.

In this study, magnetic iron oxide nanoparticles coated with heparin (Hep-MION) were synthesized and the transcellular transport of the nanoparticles across epithelial cell monolayers on porous polyester membranes was investigated. An externally applied magnetic field facilitated the transport of the Hep-MION across cell monolayers. However, high Hep-MION concentrations led to an increased aggregation of nanoparticles on the cell monolayer after application of the magnetic field. Our results indicate that magnetic guidance of Hep-MION most effectively promotes transcellular transport under conditions that minimize formation of magnetically-induced nanoparticle aggregates. Across cell monolayers, the magnet’s attraction led to the greatest increase in mass transport rate in dilute dispersions and in high serum concentrations, suggesting that magnetic guidance may be useful for in vivo targeting of Hep-MION. Full article

(This article belongs to the Special Issue What's on Board in Pharmaceutics)

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432 KiB

Open AccessArticle

Radiolabelling of Antigen and Liposomes for Vaccine Biodistribution Studies

by Malou Henriksen-Lacey, Vincent Bramwell and Yvonne Perrie

Pharmaceutics 2010, 2(2), 91-104; https://doi.org/10.3390/pharmaceutics2020091 - 31 Mar 2010

Cited by 13 | Viewed by 8567

Abstract

A relatively simple and effective method to follow the movement of pharmaceutical preparations such as vaccines in biodistribution studies is to radiolabel the components. Whilst single radiolabelling is common practice, in vaccine systems containing adjuvants the ability to follow both the adjuvant and [...] Read more.

A relatively simple and effective method to follow the movement of pharmaceutical preparations such as vaccines in biodistribution studies is to radiolabel the components. Whilst single radiolabelling is common practice, in vaccine systems containing adjuvants the ability to follow both the adjuvant and the antigen is favourable. To this end, we have devised a dual-radiolabelling method whereby the adjuvant (liposomes) is labelled with ³H and the antigen (a subunit protein) with ¹²⁵I. This model is stable and reproducible; we have shown release of the radiolabels to be negligible over periods of up to 1 week in foetal calf serum at 37 ºC. In this paper we describe the techniques which enable the radiolabelling of various components, assessing stability and processing of samples which all for their application in biodistribution studies. Furthermore we provide examples derived from our studies using this model in tuberculosis vaccine biodistribution studies. Full article

(This article belongs to the Special Issue What's on Board in Pharmaceutics)

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329 KiB

Open AccessArticle

The Effects of Pregnenolone 16α-Carbonitrile Dosing on Digoxin Pharmacokinetics and Intestinal Absorption in the Rat

by Simon Lowes, Iain S. Haslam, Britt-Marie Fihn, Constanze Hilgendorf, Johan E. Karlsson, Nicholas L. Simmons and Anna-Lena Ungell

Pharmaceutics 2010, 2(1), 61-77; https://doi.org/10.3390/pharmaceutics2010061 - 15 Mar 2010

Cited by 4 | Viewed by 11119

Abstract

The effect of Pgp induction in rats by pregnenolone 16α-carbonitrile (PCN) (3 days, 35 mg/kg/d, p.o.) on digoxin pharmacokinetics and intestinal transport has been assessed. After intravenous or oral digoxin dosing the arterial and hepatic portal vein (oral) AUC_(0-24h) were significantly reduced [...] Read more.

The effect of Pgp induction in rats by pregnenolone 16α-carbonitrile (PCN) (3 days, 35 mg/kg/d, p.o.) on digoxin pharmacokinetics and intestinal transport has been assessed. After intravenous or oral digoxin dosing the arterial and hepatic portal vein (oral) AUC_(0-24h) were significantly reduced by PCN pre-treatment. Biliary digoxin clearance increased 2-fold following PCN treatment. PCN significantly increased net digoxin secretion (2.05- and 4.5-fold respectively) in ileum and colon but not in duodenum or jejunum. This increased secretion correlated with increased Pgp protein expression in ileum and colon. Both intestinal and biliary excretion therefore contribute to altered digoxin disposition following PCN. Full article

(This article belongs to the Special Issue What's on Board in Pharmaceutics)

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107 KiB

Open AccessArticle

Ingredient Consistency of Commercially Available Polyphenol and Tocopherol Nutraceuticals

by Connie M. Remsberg, Renee L. Good and Neal M. Davies

Pharmaceutics 2010, 2(1), 50-60; https://doi.org/10.3390/pharmaceutics2010050 - 8 Mar 2010

Cited by 7 | Viewed by 7191

Abstract

Label claims of vitamin E succinate and polyphenolic nutraceuticals are assessed. A validated HPLC method was utilized to assess vitamin E succinate products. Three novel LC/MS methods were used to assess the polyphenols, pterostilbene, phloretin, and myricetin, in dietary supplements. The amount of [...] Read more.

Label claims of vitamin E succinate and polyphenolic nutraceuticals are assessed. A validated HPLC method was utilized to assess vitamin E succinate products. Three novel LC/MS methods were used to assess the polyphenols, pterostilbene, phloretin, and myricetin, in dietary supplements. The amount of vitamin E succinate varied from 0-130% of the stated label content with two products containing vitamin E acetate rather than vitamin E succinate. Expected polyphenols were found in 7 of the 8 supplement products. None of the polyphenol supplements contained content within 100-120% of label claims. The present study indicates a lack of uniformity in nutraceutical products. Full article

(This article belongs to the Special Issue What's on Board in Pharmaceutics)

1392 KiB

Open AccessArticle

Quantification of Process Induced Disorder in Milled Samples Using Different Analytical Techniques

by Ulrike Zimper, Jaakko Aaltonen, Cushla M. McGoverin, Keith C. Gordon, Karen Krauel-Goellner and Thomas Rades

Pharmaceutics 2010, 2(1), 30-49; https://doi.org/10.3390/pharmaceutics2010030 - 16 Feb 2010

Cited by 38 | Viewed by 11867

Abstract

The aim of this study was to compare three different analytical methods to detect and quantify the amount of crystalline disorder/ amorphousness in two milled model drugs. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and Raman spectroscopy were used as analytical methods [...] Read more.

The aim of this study was to compare three different analytical methods to detect and quantify the amount of crystalline disorder/ amorphousness in two milled model drugs. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and Raman spectroscopy were used as analytical methods and indomethacin and simvastatin were chosen as the model compounds. These compounds partly converted from crystalline to disordered forms by milling. Partial least squares regression (PLS) was used to create calibration models for the XRPD and Raman data, which were subsequently used to quantify the milling-induced crystalline disorder/ amorphousness under different process conditions. In the DSC measurements the change in heat capacity at the glass transition was used for quantification. Differently prepared amorphous indomethacin standards (prepared by either melt quench cooling or cryo milling) were compared by principal component analysis (PCA) to account for the fact that the choice of standard ultimately influences the quantification outcome. Finally, the calibration models were built using binary mixtures of crystalline and quench cooled amorphous drug materials. The results imply that the outcome with respect to crystalline disorder for milled drugs depends on the analytical method used and the calibration standard chosen as well as on the drug itself. From the data presented here, it appears that XRPD tends to give a higher percentage of crystalline disorder than Raman spectroscopy and DSC for the same samples. For the samples milled under the harshest milling conditions applied (60 min, sixty 4 mm balls, 25 Hz) a crystalline disorder/ amorphous content of 44.0% (XRPD), 10.8% (Raman spectroscopy) and 17.8% (DSC) were detected for indomethacin. For simvastatin 18.3% (XRPD), 15.5% (Raman spectroscopy) and 0% (DSC, no glass transition) crystalline disorder/ amorphousness were detected. Full article

(This article belongs to the Special Issue What's on Board in Pharmaceutics)

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159 KiB

Open AccessArticle

Investigation of Formulation and Process of Lyophilised Orally Disintegrating Tablet (ODT) Using Novel Amino Acid Combination

by Farhan AlHusban, Amr M. ElShaer, Jiteen H. Kansara, Alan M. Smith, Liam M. Grover, Yvonne Perrie and Afzal R. Mohammed

Pharmaceutics 2010, 2(1), 1-17; https://doi.org/10.3390/pharmaceutics2010001 - 4 Jan 2010

Cited by 17 | Viewed by 9114

Abstract

Lyophilised orally disintegrating tablets (ODTs) have achieved a great success in overcoming dysphagia associated with conventional solid dosage forms. However, the extensive use of saccharides within the formulation limits their use in treatment of chronic illnesses. The current study demonstrates the feasibility of [...] Read more.

Lyophilised orally disintegrating tablets (ODTs) have achieved a great success in overcoming dysphagia associated with conventional solid dosage forms. However, the extensive use of saccharides within the formulation limits their use in treatment of chronic illnesses. The current study demonstrates the feasibility of using combination of proline and serine to formulate zero sacharide ODTs and investigates the effect of freezing protocol on sublimation rate and tablets characteristics. The results showed that inclusion of proline and serine improved ODT properties when compared to individual counterparts. Additionally, annealing the ODTs facilitated the sublimation process and shortened the disintegration time. Full article

(This article belongs to the Special Issue What's on Board in Pharmaceutics)

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