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Molecular Pharmaceutics May 2016Opalescence in protein solutions reduces aesthetic appeal of a formulation and can be an indicator of the presence of aggregates or precursor to phase separation in... (Review)
Review
Opalescence in protein solutions reduces aesthetic appeal of a formulation and can be an indicator of the presence of aggregates or precursor to phase separation in solution signifying reduced product stability. Liquid-liquid phase separation of a protein solution into a protein-rich and a protein-poor phase has been well-documented for globular proteins and recently observed for monoclonal antibody solutions, resulting in physical instability of the formulation. The present review discusses opalescence and liquid-liquid phase separation (LLPS) for therapeutic protein formulations. A brief discussion on theoretical concepts based on thermodynamics, kinetics, and light scattering is presented. This review also discusses theoretical concepts behind intense light scattering in the vicinity of the critical point termed as "critical opalescence". Both opalescence and LLPS are affected by the formulation factors including pH, ionic strength, protein concentration, temperature, and excipients. Literature reports for the effect of these formulation factors on attractive protein-protein interactions in solution as assessed by the second virial coefficient (B2) and the cloud-point temperature (Tcloud) measurements are also presented. The review also highlights pharmaceutical implications of LLPS in protein solutions.
Topics: Antibodies, Monoclonal; Chemistry, Pharmaceutical; Humans; Hydrogen-Ion Concentration; Iridescence; Osmolar Concentration; Pharmaceutical Solutions; Proteins; Solutions; Temperature; Thermodynamics
PubMed: 27017836
DOI: 10.1021/acs.molpharmaceut.5b00937 -
The Cochrane Database of Systematic... Oct 2018Biocompatible peritoneal dialysis (PD) solutions, including neutral pH, low glucose degradation product (GDP) solutions and icodextrin, have previously been shown to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Biocompatible peritoneal dialysis (PD) solutions, including neutral pH, low glucose degradation product (GDP) solutions and icodextrin, have previously been shown to favourably influence some patient-level outcomes, albeit based on generally sub-optimal quality studies. Several additional randomised controlled trials (RCT) evaluating biocompatible solutions in PD patients have been published recently. This is an update of a review first published in 2014.
OBJECTIVES
This review aimed to look at the benefits and harms of biocompatible PD solutions in comparison to standard PD solutions in patients receiving PD.
SEARCH METHODS
The Cochrane Kidney and Transplant Specialised Register was searched up to 12 February 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
All RCTs and quasi-RCTs in adults and children comparing the effects of biocompatible PD solutions (neutral pH, lactate-buffered, low GDP; neutral pH, bicarbonate(± lactate)-buffered, low GDP; glucose polymer (icodextrin)) in PD were included. Studies of amino acid-based solutions were excluded.
DATA COLLECTION AND ANALYSIS
Two authors extracted data on study quality and outcomes. Summary effect estimates were obtained using a random-effects model, and results were expressed as risk ratios and 95% confidence intervals (CI) for categorical variables, and mean differences (MD) or standardised mean differences (SMD) and 95% CI for continuous variables.
MAIN RESULTS
This review update included 42 eligible studies (3262 participants), including six new studies (543 participants). Overall, 29 studies (1971 participants) compared neutral pH, low GDP PD solution with conventional PD solution, and 13 studies (1291 participants) compared icodextrin with conventional PD solution. Risk of bias was assessed as high for sequence generation in three studies, allocation concealment in three studies, attrition bias in 21 studies, and selective outcome reporting bias in 16 studies.Neutral pH, low GDP versus conventional glucose PD solutionUse of neutral pH, low GDP PD solutions improved residual renal function (RRF) preservation (15 studies, 835 participants: SMD 0.19, 95% CI 0.05 to 0.33; high certainty evidence). This approximated to a mean difference in glomerular filtration rate of 0.54 mL/min/1.73 m (95% CI 0.14 to 0.93). Better preservation of RRF was evident at all follow-up durations with progressively greater preservation observed with increasing follow up duration. Neutral pH, low GDP PD solution use also improved residual urine volume preservation (11 studies, 791 participants: MD 114.37 mL/day, 95% CI 47.09 to 181.65; high certainty evidence). In low certainty evidence, neutral pH, low GDP solutions may make little or no difference to 4-hour peritoneal ultrafiltration (9 studies, 414 participants: SMD -0.42, 95% CI -0.74 to -0.10) which approximated to a mean difference in peritoneal ultrafiltration of 69.72 mL (16.60 to 122.00 mL) lower, and may increase dialysate:plasma creatinine ratio (10 studies, 746 participants: MD 0.01, 95% CI 0.00 to 0.03), technique failure or death compared with conventional PD solutions. It is uncertain whether neutral pH, low GDP PD solution use led to any differences in peritonitis occurrence, hospitalisation, adverse events (6 studies, 519 participants) or inflow pain (1 study, 58 participants: RR 0.51, 95% CI 0.24 to 1.08).Glucose polymer (icodextrin) versus conventional glucose PD solutionIn moderate certainty evidence, icodextrin probably reduced episodes of uncontrolled fluid overload (2 studies, 100 participants: RR 0.30, 95% CI 0.15 to 0.59) and augmented peritoneal ultrafiltration (4 studies, 102 participants: MD 448.54 mL/d, 95% CI 289.28 to 607.80) without compromising RRF (4 studies, 114 participants: SMD 0.12, 95% CI -0.26 to 0.49; low certainty evidence) which approximated to a mean creatinine clearance of 0.30 mL/min/1.73m higher (0.65 lower to 1.23 higher) or urine output (3 studies, 69 participants: MD -88.88 mL/d, 95% CI -356.88 to 179.12; low certainty evidence). It is uncertain whether icodextrin use led to any differences in adverse events (5 studies, 816 participants) technique failure or death.
AUTHORS' CONCLUSIONS
This updated review strengthens evidence that neutral pH, low GDP PD solution improves RRF and urine volume preservation with high certainty. These effects may be related to increased peritoneal solute transport and reduced peritoneal ultrafiltration, although the evidence for these outcomes is of low certainty due to significant heterogeneity and suboptimal methodological quality. Icodextrin prescription increased peritoneal ultrafiltration and mitigated uncontrolled fluid overload with moderate certainty. The effects of either neutral pH, low GDP solution or icodextrin on peritonitis, technique survival and patient survival remain uncertain and require further high quality, adequately powered RCTs.
Topics: Adult; Bicarbonates; Child; Dialysis Solutions; Glucose; Humans; Hydrogen-Ion Concentration; Icodextrin; Kidney; Peritoneal Dialysis; Peritoneum; Pharmaceutical Solutions; Randomized Controlled Trials as Topic; Urine
PubMed: 30362116
DOI: 10.1002/14651858.CD007554.pub3 -
International Journal of Pharmaceutical... 2016Ready-to-use solutions are the most preferable and most common dosage forms for injectable and topical ophthalmic products. Drugs formulated as solution almost always...
Ready-to-use solutions are the most preferable and most common dosage forms for injectable and topical ophthalmic products. Drugs formulated as solution almost always have chemical and physical stability challenges as well as solubility limitations and the need to prevent inadvertent microbial contamination issues. The first in this series of articles took us through a discussion of optimizing the physical stability of solutions. This article concludes this series of articles with a discussion on foreign particles, protein aggregation, and immunogenicity; optimizing microbiological activity; and osmolality (tonicity) agents, and discusses how these challenges and issues are addressed.
Topics: Adsorption; Chemistry, Pharmaceutical; Drug Stability; Pharmaceutical Solutions; Preservatives, Pharmaceutical; Protein Aggregates; Solutions
PubMed: 27326440
DOI: No ID Found -
Vox Sanguinis Jul 2006Anticoagulant and nutrient solutions allow red blood cells to be stored and transported, enabling modern blood banking. The development of these solutions has been slow,... (Review)
Review
Anticoagulant and nutrient solutions allow red blood cells to be stored and transported, enabling modern blood banking. The development of these solutions has been slow, covering 90 years, and the reasons for past formulations are best understood in a historical context. Modern red cell storage solutions work well for blood banks, allowing 5-7-week storage, which means more than 90% of collected units find a recipient. Improved scientific understanding of the red cell storage lesion has shown a way to make even better storage solutions, which maintain red cell metabolism and reduce membrane loss.
Topics: Blood Banks; Blood Preservation; Erythrocytes; History, 20th Century; History, 21st Century; Humans; Pharmaceutical Solutions
PubMed: 16756596
DOI: 10.1111/j.1423-0410.2006.00778.x -
Bioanalysis Dec 2015Clinical and Pharmaceutical Solutions through Analysis, São Paulo, Brazil, 3-5 August 2015 The 2nd Annual Symposium on Clinical and Pharmaceutical Solutions through...
Clinical and Pharmaceutical Solutions through Analysis (CPSA BRASIL 2015): on the way to innovation - pharmaceutical/analytical technology, regulation and knowledge management.
Clinical and Pharmaceutical Solutions through Analysis, São Paulo, Brazil, 3-5 August 2015 The 2nd Annual Symposium on Clinical and Pharmaceutical Solutions through Analysis was held on 3-5 August 2015 at Club Transatlântico, São Paulo, Brazil. This annual meeting began in 2014 and was the first industry-led event in Brazil to focus on the specific needs of industry researchers while bringing together technology and regulators. The goal of CPSA is to provide an in-depth review of innovative technology and industry practices through open discussion of industry-related issues and needs. Education and specialized training are the foundation of all CPSA events. As the industry has evolved so has CPSA. The CPSA annual meeting thrived with high quality scientific content, open interaction from industry opinion leaders and a collegial environment.
Topics: Brazil; Drug Discovery; Drug Industry; History, 21st Century; Humans; Knowledge Management; Pharmaceutical Solutions
PubMed: 26617112
DOI: 10.4155/bio.15.216 -
Journal of Pharmaceutical and... Jan 2018Vibrational and X-ray spectroscopic techniques are based on the interaction between radiation and matter. This interaction produces various signals that can be detected...
Forensic investigation in the pharmaceutical industry: Identification procedure of visible particles in (drug) solutions and different containers by combining vibrational and X-ray spectroscopic techniques.
Vibrational and X-ray spectroscopic techniques are based on the interaction between radiation and matter. This interaction produces various signals that can be detected and that contain information about the morphology, structure or composition of molecules analyzed. When combined together, these complementary techniques are very powerful and facilitate the identification of the samples investigated. Nevertheless, prior sample preparation plays an important role in this identification, since it should allow combining analytical methods without damaging the samples. Through 5 case studies involving visible particles found in various containers, this article shows how an accurate sample preparation procedure associated to a combination of Infrared, Raman and energy dispersive X-ray (EDX) spectroscopies applies for the troubleshooting of foreign matters in pharmaceutical drug products. The forensic investigation procedure proved to be successful for the precise identification of samples.
Topics: Drug Industry; Pharmaceutical Solutions; Spectrophotometry, Infrared; Spectrum Analysis, Raman; Vibration; X-Rays
PubMed: 29080414
DOI: 10.1016/j.jpba.2017.10.015 -
Drug Development and Industrial Pharmacy 2016The influence of pH on the stability of cefozopran hydrochloride (CZH) was investigated in the pH range of 0.44-13.00. Six degradation products were identified with a...
The influence of pH on the stability of cefozopran hydrochloride (CZH) was investigated in the pH range of 0.44-13.00. Six degradation products were identified with a hybrid ESI-Q-TOF mass spectrometer. The degradation of CZH as a result of hydrolysis was a pseudo-first-order reaction. As general acid-base hydrolysis of CZH was not occurred in the solutions of hydrochloric acid, sodium hydroxide, acetate, borate and phosphate buffers, kobs = kpH because specific acid-base catalysis was observed. Specific acid-base catalysis of CZH consisted of the following reactions: hydrolysis of CZH catalyzed by hydrogen ions (kH+), hydrolysis of dications (k1H2O), monocations (k2H2O) and zwitter ions (k3H2O) and hydrolysis of zwitter ions (k1OH-) and monoanions (k2OH-) of CZH catalyzed by hydroxide ions. The total rate of the reaction was equal to the sum of partial reactions: [Formula: see text]. CZH similarly like other fourth generation cephalosporin was most stable at slightly acidic and neutral pH and less stable in alkaline pH. The cleavage of the β-lactam ring resulting from a nucleophilic attack on the carbonyl carbon in the β-lactam moiety is the preferred degradation pathway of β-lactam antibiotics in aqueous solutions.
Topics: Cephalosporins; Drug Stability; Hydrogen-Ion Concentration; Pharmaceutical Solutions; Water; Cefozopran
PubMed: 26079426
DOI: 10.3109/03639045.2015.1054834 -
Current Pharmaceutical Biotechnology Jun 2005A great number of pharmaceutical substances exist in crystalline solid-state. Because of the complexity of their chemical structure many different polymorphs of a given... (Review)
Review
A great number of pharmaceutical substances exist in crystalline solid-state. Because of the complexity of their chemical structure many different polymorphs of a given substance can exist. Polymorphic forms of solid pharmaceuticals influence not only their dissolution behavior, i.e. bioavailability but also their solid-state stability. It is well known that only one polymorphic form is thermodynamically stable and all other metastable forms will convert, eventually, to the more stable form. Hence it is essential to choose the most suitable polymorphic form in the early stage of pharmaceutical development. The following article reviews the recent applications of solution calorimetry that allows characterization of pharmaceutical polymorphs through accurate determination of enthalpy of solution. Each crystalline form possesses a defined enthalpy of solution, therefore solution calorimetry is used for the quantitative analysis of the desired polymorphic form and determination of enthalpy of transition corresponding to the difference in enthalpies of solution for a polymorphic pair. More recently this technique has been applied to the estimation of thermodynamic transition temperature, which is useful for the evaluation of thermodynamic stability relationships between polymorphs. This article will also describe the kinetics and thermodynamics of polymorphic transitions, from a metastable form to the thermodynamically stable form, through studies using ampoule-based isothermal microcalorimetry. Such studies are particularly useful when metastable forms are to be selected in order to enhance bioavailability. If the metastable form, or the pharmaceutical product containing it, can be shown to be sufficiently stable, it could then be used in a formulation where its therapeutic effects could be exploited.
Topics: Calorimetry; Isomerism; Pharmaceutical Preparations; Pharmaceutical Solutions; Reproducibility of Results; Thermodynamics
PubMed: 15974974
DOI: 10.2174/1389201054022904 -
Current Pharmaceutical Biotechnology Jun 2005In solution calorimetry the heat of solution (Delta(sol)H) is recorded as a solute (usually a solid) dissolves in an excess of solvent. Such measurements are valuable... (Review)
Review
In solution calorimetry the heat of solution (Delta(sol)H) is recorded as a solute (usually a solid) dissolves in an excess of solvent. Such measurements are valuable during all the phases of pharmaceutical formulation and the number of applications of the technique is growing. For instance, solution calorimetry is extremely useful during preformulation for the detection and quantification of polymorphs, degrees of crystallinity and percent amorphous content; knowledge of all of these parameters is essential in order to exert control over the manufacture and subsequent performance of a solid pharmaceutical. Careful experimental design and data interpretation also allows the measurement of the enthalpy of transfer (Delta(trans)H) of a solute between two phases. Because solution calorimetry does not require optically transparent solutions, and can be used to study cloudy or turbid solutions or suspensions directly, measurement of Delta(trans)H affords the opportunity to study the partitioning of drugs into, and across, biological membranes. It also allows the in-situ study of cellular systems. Furthermore, novel experimental methodologies have led to the increasing use of solution calorimetry to study a wider range of phenomena, such as the precipitation of drugs from supersaturated solutions or the formation of liposomes from phospholipid films. It is the purpose of this review to discuss some of these applications, in the context of pharmaceutical formulation and preformulation, and highlight some of the potential future areas where solution calorimetry might find applications.
Topics: Algorithms; Biological Products; Calorimetry; Isomerism; Pharmaceutical Solutions
PubMed: 15974976
DOI: 10.2174/1389201054022887 -
The Medical Letter on Drugs and... Jul 2011The Medical Letter recently reviewed a topical gel formulation of testosterone (Fortesta) for treatment of hypogonadism in men. A topical testosterone replacement... (Review)
Review
The Medical Letter recently reviewed a topical gel formulation of testosterone (Fortesta) for treatment of hypogonadism in men. A topical testosterone replacement product for application to the axilla, Axiron (Lilly) solution, has now become available for the same indication. This site of application presumably minimizes the risk of transferring the drug to a family member or sexual partner.
Topics: Administration, Topical; Animals; Clinical Trials as Topic; Exanthema; Humans; Hypogonadism; Male; Pharmaceutical Solutions; Testosterone
PubMed: 21738108
DOI: No ID Found