Recent items - Journal of Pharmaceutical Sciences
Comparative assessment of empirical and physiological approaches on predicting human clearances
10/09/2010 01:53
The empirical and physiological predictive approaches to human clearance were evaluated using preclinical in vitro and in vivo data of various datasets to establish a methodology for the prediction of clearance. Among the examined empirical approaches, an allometric scaling method with the rule of exponent (ROE), based on the exponent in simple allometry, provided better prediction. The effect of lipophilicity (clog P) and clearance on the predictivity was investigated using the ROE method. High [...]
10/09/2010 01:53
The empirical and physiological predictive approaches to human clearance were evaluated using preclinical in vitro and in vivo data of various datasets to establish a methodology for the prediction of clearance. Among the examined empirical approaches, an allometric scaling method with the rule of exponent (ROE), based on the exponent in simple allometry, provided better prediction. The effect of lipophilicity (clog P) and clearance on the predictivity was investigated using the ROE method. High [...]
Development of quality‐by‐design analytical methods
10/09/2010 01:53
Quality‐by‐design (QbD) is a systematic approach to drug development, which begins with predefined objectives, and uses science and risk management approaches to gain product and process understanding and ultimately process control. The concept of QbD can be extended to analytical methods. QbD mandates the definition of a goal for the method, and emphasizes thorough evaluation and scouting of alternative methods in a systematic way to obtain optimal method performance. Candidate methods are then [...]
10/09/2010 01:53
Quality‐by‐design (QbD) is a systematic approach to drug development, which begins with predefined objectives, and uses science and risk management approaches to gain product and process understanding and ultimately process control. The concept of QbD can be extended to analytical methods. QbD mandates the definition of a goal for the method, and emphasizes thorough evaluation and scouting of alternative methods in a systematic way to obtain optimal method performance. Candidate methods are then [...]
Rapid characterization of glycosaminoglycans using a combined approach by infrared and Raman microspectroscopies
07/09/2010 02:13
This study describes a complementary infrared (IR) and Raman spectroscopic investigations of a set of biomolecule representatives of glycosaminoglycans (GAGs) class. Both IR and Raman data exhibit characteristic spectral signatures that allow a direct molecular distinction of these compounds. Comparison of these molecular signatures clearly evidences the differences between heparan sulfate and heparin by computing the intensity ratio between the 1248 cm−1 and 1043 cm−1 peaks, corresponding respe [...]
07/09/2010 02:13
This study describes a complementary infrared (IR) and Raman spectroscopic investigations of a set of biomolecule representatives of glycosaminoglycans (GAGs) class. Both IR and Raman data exhibit characteristic spectral signatures that allow a direct molecular distinction of these compounds. Comparison of these molecular signatures clearly evidences the differences between heparan sulfate and heparin by computing the intensity ratio between the 1248 cm−1 and 1043 cm−1 peaks, corresponding respe [...]
Development of inhalable nanocrystalline solid dispersion of Tranilast for airway inflammatory diseases
07/09/2010 02:13
Tranilast (TL), an antiallergic agent, has been clinically used in the treatment of bronchial asthma, although the clinical use of TL is limited because of its poor solubility and systemic side effects. To overcome these drawbacks, a novel respirable powder (RP) of TL for inhalation therapy was developed using nanocrystal solid dispersion of TL (CSD/TL). In the CSD/TL, wet‐milled crystalline TL particles with a mean diameter of 122 nm were dispersed, and there was a marked improvement in dissolu [...]
07/09/2010 02:13
Tranilast (TL), an antiallergic agent, has been clinically used in the treatment of bronchial asthma, although the clinical use of TL is limited because of its poor solubility and systemic side effects. To overcome these drawbacks, a novel respirable powder (RP) of TL for inhalation therapy was developed using nanocrystal solid dispersion of TL (CSD/TL). In the CSD/TL, wet‐milled crystalline TL particles with a mean diameter of 122 nm were dispersed, and there was a marked improvement in dissolu [...]
Monoclonal antibody aggregation intermediates visualized by atomic force microscopy
07/09/2010 02:13
Ubiquitous but highly variable processes of therapeutic protein aggregation remain poorly characterized, especially in the context of common infusion reactions and clinical immunogenicity. Among the numerous challenges is the characterization of intermediate steps that lead to the appearance of precipitates. Although the biophysical methods for elucidation of secondary and tertiary structures as well as overall size distribution are typically well established in the development laboratories, the [...]
07/09/2010 02:13
Ubiquitous but highly variable processes of therapeutic protein aggregation remain poorly characterized, especially in the context of common infusion reactions and clinical immunogenicity. Among the numerous challenges is the characterization of intermediate steps that lead to the appearance of precipitates. Although the biophysical methods for elucidation of secondary and tertiary structures as well as overall size distribution are typically well established in the development laboratories, the [...]
Monitoring the viscoelastic properties of skin in liquid environments using quartz crystal microbalance
07/09/2010 02:13
Quartz crystal microbalance (QCM) with dissipation can be used to measure the response of the human stratum corneum (SC) attached to the QCM crystal, as it adsorbs or desorbs active ingredients from a liquid medium. The method was demonstrated with the sorption of poly(diallyl dimethyl ammonium chloride), a cationic polymer widely used in formulations for topical and transdermal applications. Using 14‐mm diameter SC coupons attached to the QCM crystals with an adhesive, up to five overtones (up [...]
07/09/2010 02:13
Quartz crystal microbalance (QCM) with dissipation can be used to measure the response of the human stratum corneum (SC) attached to the QCM crystal, as it adsorbs or desorbs active ingredients from a liquid medium. The method was demonstrated with the sorption of poly(diallyl dimethyl ammonium chloride), a cationic polymer widely used in formulations for topical and transdermal applications. Using 14‐mm diameter SC coupons attached to the QCM crystals with an adhesive, up to five overtones (up [...]
Biocompatibility of an injectable in situ forming depot for peptide delivery
06/09/2010 02:34
Poly(ethyleneglycol) 500 dimethylether (PEG500DME) was tested as a novel solvent for the manufacture of an injectable in situ forming depot (ISFD) containing poly(D,L‐lactide‐co‐glycolide) (PLGA). The sustained release of pasireotide from the ISFD was evaluated in vitro and in vivo. Furthermore, the local tolerability of the delivery system using PEG500DME was investigated in subcutaneous (s.c.) tissue over 48 days. A flow‐through cell was used to determine the in vitro drug release from the ISF [...]
06/09/2010 02:34
Poly(ethyleneglycol) 500 dimethylether (PEG500DME) was tested as a novel solvent for the manufacture of an injectable in situ forming depot (ISFD) containing poly(D,L‐lactide‐co‐glycolide) (PLGA). The sustained release of pasireotide from the ISFD was evaluated in vitro and in vivo. Furthermore, the local tolerability of the delivery system using PEG500DME was investigated in subcutaneous (s.c.) tissue over 48 days. A flow‐through cell was used to determine the in vitro drug release from the ISF [...]
Optimized microemulsions and solid microemulsion systems of simvastatin: Characterization and in vivo evaluation
05/09/2010 03:25
05/09/2010 03:25
Theophylline‐loaded compritol microspheres prepared by ultrasound‐assisted atomization
02/09/2010 23:57
02/09/2010 23:57
Latent structure analysis in pharmaceutical formulations using Kohonen's self‐organizing map and a Bayesian network
01/09/2010 00:13
01/09/2010 00:13
Fabrication of paclitaxel nanocrystals by femtosecond laser ablation and fragmentation
31/08/2010 21:21
31/08/2010 21:21
Customized in silico population mimics actual population in docetaxel population pharmacokinetic analysis
28/08/2010 00:25
28/08/2010 00:25
Understanding size enlargement and hardening of granules on tabletability of unlubricated granules prepared by dry granulation
28/08/2010 00:25
28/08/2010 00:25
Degradation of polysorbates 20 and 80: Studies on thermal autoxidation and hydrolysis
28/08/2010 00:25
28/08/2010 00:25
Structural transformations of polycomplex matrices based on countercharged (meth)acrylate copolymers
28/08/2010 00:25
28/08/2010 00:25
Poloxamer/cyclodextrin/chitosan‐based thermoreversible gel for intranasal delivery of fexofenadine hydrochloride
27/08/2010 18:45
27/08/2010 18:45
Thermosensitive hydrogels composed of hyaluronic acid and gelatin as carriers for the intravesical administration of cisplatin
27/08/2010 00:22
27/08/2010 00:22
A reliable predictive factorial model for entrapment optimization of a sodium bisphosphonate into biodegradable microspheres
27/08/2010 00:22
27/08/2010 00:22
Production of pH‐responsive microparticles by spray drying: Investigation of experimental parameter effects on morphological and release properties
27/08/2010 00:22
27/08/2010 00:22
Influence of Pluronic® F68 on ceftazidime biological activity in parenteral solutions
27/08/2010 00:22
27/08/2010 00:22
Alteration in the pharmacokinetics of hemoglobin‐vesicles in a rat model of chronic liver cirrhosis is associated with kupffer cell phagocyte activity
27/08/2010 00:22
27/08/2010 00:22
Attaching zanamivir to a polymer markedly enhances its activity against drug‐resistant strains of influenza a virus
26/08/2010 02:05
26/08/2010 02:05
Detection of free base surface enrichment of a pharmaceutical salt by X‐ray photoelectron spectroscopy (XPS)
26/08/2010 02:05
26/08/2010 02:05
Impact of the trade‐related aspects of intellectual property rights (TRIPS) agreement on India as a supplier of generic antiretrovirals
26/08/2010 02:05
26/08/2010 02:05
A new approach to determine camptothecin and its analogues affinity to human serum albumin
25/08/2010 23:18
25/08/2010 23:18
A three‐dimensional polycaprolactone scaffold combined with a drug delivery system consisting of electrospun nanofibers
25/08/2010 23:18
25/08/2010 23:18
Controlled drug delivery system based on ordered mesoporous silica matrices of captopril as angiotensin‐converting enzyme inhibitor drug
25/08/2010 23:18
25/08/2010 23:18
Vaccines with aluminum‐containing adjuvants: Optimizing vaccine efficacy and thermal stability
25/08/2010 23:18
25/08/2010 23:18
Application of extrinsic fluorescence spectroscopy for the high throughput formulation screening of aluminum‐adjuvanted vaccines
25/08/2010 23:18
25/08/2010 23:18
Oral apomorphine delivery from solid lipid nanoparticleswith different monostearate emulsifiers: Pharmacokineticand behavioral evaluations
25/08/2010 23:18
25/08/2010 23:18
A thermodynamic‐based approach to analyzing a highly solvating polymorphic system: The desolvation window method
25/08/2010 04:19
25/08/2010 04:19
Composite fiber structures with antiproliferative agents exhibit advantageous drug delivery and cell growth inhibition in vitro
24/08/2010 04:43
24/08/2010 04:43
Formulation and evaluation of quercetin polycaprolactone microspheres for the treatment of rheumatoid arthritis
22/08/2010 03:12
22/08/2010 03:12
Biowaiver monographs for immediate release solid oral dosage forms: Ciprofloxacin hydrochloride
18/08/2010 02:43
18/08/2010 02:43
The study of phase separation in amorphous freeze‐dried systems. part I: Raman mapping and computational analysis of XRPD data in model polymer systems
18/08/2010 02:43
18/08/2010 02:43
Development of respirable nanomicelle carriers for delivery of amphotericin B by jet nebulization
18/08/2010 02:43
18/08/2010 02:43
Biowaiver monographs for immediate release solid oral dosage forms: mefloquine hydrochloride
18/08/2010 02:43
18/08/2010 02:43
Preparation of uniform‐sized multiple emulsions and micro/nano particulates for drug delivery by membrane emulsification
15/08/2010 01:19
15/08/2010 01:19
Drug delivery trends in clinical trials and translational medicine: Evaluation of pharmacokinetic properties in special populations
15/08/2010 01:19
15/08/2010 01:19
Terminology challenges: Defining modified release dosage forms in veterinary medicine
13/08/2010 12:44
Terminologies for describing dosage form release characteristics for human pharmaceuticals have been addressed by bodies such as the US Food and Drug Administration (FDA), the International Conference on Harmonization (ICH), and the US Pharmacopeia (USP). While the definition for terms such as “immediate release,” “modified release,” “extended release,” and “delayed release” are now well accepted for human pharmaceuticals, confusion still exists within the veterinary community. In part, this con [...]
13/08/2010 12:44
Terminologies for describing dosage form release characteristics for human pharmaceuticals have been addressed by bodies such as the US Food and Drug Administration (FDA), the International Conference on Harmonization (ICH), and the US Pharmacopeia (USP). While the definition for terms such as “immediate release,” “modified release,” “extended release,” and “delayed release” are now well accepted for human pharmaceuticals, confusion still exists within the veterinary community. In part, this con [...]
Review of the basic and clinical pharmacology of sulfobutylether‐β‐cyclodextrin (SBECD)
13/08/2010 12:44
Despite its use in commercially available drugs such as intravenous voriconazole, there is little known in the medical literature about the clinical pharmacology of the solubilizing agent, sulfobutylether‐β‐cyclodextrin (SBECD). This paper summarizes all known data on SBECD pharmacokinetics and safety. In animals, volume of distribution approximates extracellular water volume and clearance is determined by the glomerular filtration rate. SBECD does not have any apparent effects on cardiovascular [...]
13/08/2010 12:44
Despite its use in commercially available drugs such as intravenous voriconazole, there is little known in the medical literature about the clinical pharmacology of the solubilizing agent, sulfobutylether‐β‐cyclodextrin (SBECD). This paper summarizes all known data on SBECD pharmacokinetics and safety. In animals, volume of distribution approximates extracellular water volume and clearance is determined by the glomerular filtration rate. SBECD does not have any apparent effects on cardiovascular [...]
An industry perspective on the monitoring of subvisible particles as a quality attribute for protein therapeutics
13/08/2010 12:44
Concern around the lack of monitoring of proteinaceous subvisible particulates in the 0.1–10 µm range has been heightened (Carpenter et al., 2009, J Pharm Sci 98: 1202–1205), primarily due to uncertainty around the potential immunogenicity risk from these particles. This article, representing the opinions of a number of industry scientists, aims to further the discussion by developing a common understanding around the technical capabilities, limitations, as well as utility of monitoring this siz [...]
13/08/2010 12:44
Concern around the lack of monitoring of proteinaceous subvisible particulates in the 0.1–10 µm range has been heightened (Carpenter et al., 2009, J Pharm Sci 98: 1202–1205), primarily due to uncertainty around the potential immunogenicity risk from these particles. This article, representing the opinions of a number of industry scientists, aims to further the discussion by developing a common understanding around the technical capabilities, limitations, as well as utility of monitoring this siz [...]
Roles of granule size in over‐granulation during high shear wet granulation
13/08/2010 12:44
A mechanistic understanding of the over‐granulation problem during high shear wet granulation (HSWG) process can guide efficient development of robust formulation and manufacturing process. Using microcrystalline cellulose (MCC) as a model compound, we demonstrate that size enlargement is an important mechanism for over‐granulation in HSWG. A higher granulation water level results in larger granules and lower tabletability. With increasing water, granules enlarge sharply when water level is high [...]
13/08/2010 12:44
A mechanistic understanding of the over‐granulation problem during high shear wet granulation (HSWG) process can guide efficient development of robust formulation and manufacturing process. Using microcrystalline cellulose (MCC) as a model compound, we demonstrate that size enlargement is an important mechanism for over‐granulation in HSWG. A higher granulation water level results in larger granules and lower tabletability. With increasing water, granules enlarge sharply when water level is high [...]
Purification of PEGylated protein using membrane chromatography
13/08/2010 12:44
N‐terminus‐specific PEGylation was used to produce mono‐PEGylated lysozyme. However, some di‐ and tri‐PEGylated proteins were also produced due to side chain reaction. The reaction products were characterized by chromatographic and electrophoretic methods. Commercial cation exchange membrane Sartobind S was used for chromatographic purification of PEGylated lysozyme, the basis of separation being the shielding of protein charge by PEG. Using the membrane chromatographic method, lysozyme and mono [...]
13/08/2010 12:44
N‐terminus‐specific PEGylation was used to produce mono‐PEGylated lysozyme. However, some di‐ and tri‐PEGylated proteins were also produced due to side chain reaction. The reaction products were characterized by chromatographic and electrophoretic methods. Commercial cation exchange membrane Sartobind S was used for chromatographic purification of PEGylated lysozyme, the basis of separation being the shielding of protein charge by PEG. Using the membrane chromatographic method, lysozyme and mono [...]