Chemical Stability Of Drug Research Articles

A Snapshot on Polymeric Micelles as a Carrier for Drug Delivery

Abstract: Micellization is the process of formation of micelles using different polymers mainly plu-ronic (F127, F123, etc.). Polymers are used to formulate polymeric micelles that provide physical and chemical stability of drugs that are encapsulated into them. Moreover, the drugs are encapsulat-ed in the core portion (hydrophobic inner) of micelles and another portion is the shell portion (hy-drophilic outer) which provides hydrophilicity to the hydrophobic drug. Delivery of hydrophobic drugs by micelles is easy and preferred due to the nano size structure, well association, low toxicity, biocompatible, well core structure, and a high stability. Several methods of preparation of micelles such as - thin film hydration, solvent evaporation, dialysis, and direct dissolution are discussed here. Micelles formulations in pharmaceutical industries are preferred because they enhance the solubility and bioavailability of drugs of BCS class II and IV. This review focuses on various strategies to overcome the problems related to poor aqueous solubility and bioavailability of drugs, micellar sol-ubilization, and application of micelles for various drug delivery. It also includes future considera-tions for the development of various polymeric micelles-based drug formulations.

Welcome to Pharmaceutical Communications

Welcome to the inaugural issue of Pharmaceutical Communications-a biannual, open access, and peer-reviewed journal aiming to publish high-quality research articles in the field of basic & advanced pharmaceutics and pharmaceutical technology. Pharmaceutical Communications is a biannual, peer-reviewed journal published online and in print that primarily publishes research articles and reviews that focus on basic and advanced pharmaceutics. The journal accepts manuscripts related to but not limited to, the processing of pharmaceuticals, such as crystallization, lyophilization, chemical stability of drugs, pharmacokinetics, biopharmaceutics, pro-drug developments, metabolic disposition of bioactive agents, dosage form design, pharmaceutical technology, targeted drug delivery. Other topics include pharmaceutical marketing, pharmaceutical promotion, patient-provider communication, healthcare communication, patient safety, and innovations in the pharmaceutical industry. Pharmaceutical Communications primarily accepts original research articles and reviews. However, invited editorial summaries and letters to the editor are also occasionally published. The journal provides a platform for scientists, practitioners, and healthcare professionals to share their knowledge and experiences in the field of pharmaceutics. The journal also serves as a forum for discussing and debating current issues and trends in the pharmaceutical industry. The journal welcomes submissions from academics, practitioners, and industry professionals who wish to share their research and perspectives on topics related to pharmaceutics. In the last two decades, rapid technological advances have enabled researchers to investigate arcane technological phenomena and ask more profound questions. Several pharmaceutical processes involved in the manufacturing of various dosage forms are being unraveled at a rapid pace, high resolution, and with unprecedented details. Authors carrying out investigations leveraging these technologies dealing with the composition, formulation, preparation, or manufacturing and quality control of extemporaneously compounded or commercially manufactured drugs are encouraged to submit their findings to Pharmaceutical Communications. The purpose of this journal is to provide a platform to the scientific fraternity, especially regional and national academics, where they could get their studies published after a rapid, transparent, and high-quality peer review. All the articles published in Pharmaceutical Communications will be freely available to readers immediately after publication. The open-access policy of our journal is likely to increase the readership of articles and enhance their visibility and citation potential. The journal also welcomes submissions from authors from any country. Therefore, I invite you to submit your work to Pharmaceutical Communications. We look forward to receiving your submissions! Professor Dr. Fazli Nasir Editor-In-Chief Rehabilitation Communications

Correlation between the stability constant and pH for β-cyclodextrin complexes.

In drug formulations, cyclodextrins are used to increase aqueous solubility and chemical stability of drugs via formation of inclusion complexes. For ionizable drug molecules, the complexation strength depends on pH. Increased ionization leads to a more soluble drug, but also results in destabilization of cyclodextrin complexes. Therefore, formulation scientists aim to find a balance between increased drug solubility and high complexation strength. In this work, a theoretical expression for the dependency between the stability constant and pH is presented, allowing the accurate prediction of the stability constant at any pH. The theoretical expression requires three out of four input parameters; the pKa of the free guest molecule, the pKa of the complex, and the stability constants for the neutral and fully ionized complex. Stability constants for β-cyclodextrin and ibuprofen complexes were determined by isothermal titration calorimetry at seven pH values (2.5-5.5) and four temperatures (15-55 °C). All these measured stability constants complied with the theoretical expression. Ten additional data sets from the literature comprising eight different drug molecules and three different cyclodextrins confirmed the ability of the theoretical expression to account for the observed pH-dependence of stability constants.

Effects of the Preparation Process on the Properties of Amorphous Solid Dispersions.

The use of amorphous solid dispersions to improve the bioavailability of active ingredients from the BCS II and IV classifications continues to gain interest in the pharmaceutical industry. Over the last decade, methods for generating amorphous solid dispersions have been well established in commercially available products and in the literature. However, the amorphous solid dispersions manufactured by different technologies differ in many aspects, primarily chemical stability, physical stability, and performance, both in vitro and in vivo. This review analyzes the impact of manufacturing methods on those properties of amorphous solid dispersions. For example, the chemical stability of drugs and polymers can be influenced by differences in the level of thermal exposure during fusion-based and solvent-based processes. The physical stability of amorphous content varies according to the thermal history, particle morphology, and nucleation process of amorphous solid dispersions produced by different methods. The in vitro and in vivo performance of amorphous formulations are also affected by differences in particle morphology and in the molecular interactions caused by the manufacturing method. Additionally, we describe the mechanism of manufacturing methods and the thermodynamic theories that relate to amorphous formulations.

Effects of cyclodextrins on the chemical stability of drugs

Cyclodextrins (CDs) are enabling pharmaceutical excipients that can enhance both solubility and stability of wide variety of drugs in aqueous solutions through formation of drug/CD inclusion complexes where apolar moieties of the drug molecules are located inside the CD cavity. In properly designed pharmaceutical formulations CDs will improve physiochemical properties of lipophilic drugs without affecting their intrinsic ability to permeate biological membranes. Here the effect of CD complexes on the chemical stability of drugs is reviewed. Numerous studies shown that in aqueous solutions CD complexation can hamper hydrolysis, oxidation, photodegradation, isomerization and enzyme catalyzed degradation of dissolved drugs. However, some drugs, such as β-lactam antibiotics, can under certain conditions undergo CD catalyzed degradation in aqueous solutions. Also, some drugs that are stabilized by CDs in aqueous solutions are destabilized by the same CDs in solid dosage forms. Thus, the effects of CDs on drug stability have to be tested and verified in the final drug formulation and under the recommended storage conditions.

Electrospun gelatin nanofibers as drug carrier: effect of crosslinking on sustained release

This study aims to develop a natural biopolymer based nanofabric as an oral drug carrier to deliver a model hydrophobic drug (piperine) in a sustained and controlled manner over prolonged time. For that, we electrospun gelatin nanofabric mesh followed by crosslinking using saturated vapor of glutaraldehyde (GTA) for 8 mins to improve the water resistive properties. Later, we investigated the effect of different crosslinking strategies and found that layer-by-layer crosslinking not only provides an improved structural integrity, thermal and chemical stability of drug but also yields a tight control over sustained drug release up to 8 h.

Stability Studies of Ternary Mixtures Containing Fosaprepitant, Dexamethasone, Ondansetron and Granisetron Used in Clinical Practice

The use of a combination of 5HT3 receptor antagonist, a NK-1 receptor antagonist and dexamethasone has been classified to be state of the art in patients receiving highly as well as moderately emetogenic chemotherapy like cisplatin and anthracyclines. The administration of the ad-hoc admixture of fosaprepitant, dexamethasone and ondansetron (FDO) or granisetron (FDG) in the same IV infusion solution will improve the management of ambulatory procedures related to reducing administration time and number of administered intravenous preparations. All this would improve patient safety and comfort. In order to guarantee security of patients and efficacy of treatment, information about physico-chemical stability of both ternary mixtures at concentrations used in routine clinical practice and at different conditions of storage is needed. In this study, physico-chemical stability of ternary mixtures of fosaprepitant (150 mg), dexamethasone (8 mg) and ondansetron (8 mg) or granisetron (3 mg) in 50,100 and 250 ml of 0.9 g/dl NaCl at room temperature/refrigerated and protective from/exposed to light has been evaluated. An HPLC method has been developed and validated according to International Conference on Harmonization guidelines to evaluate chemical stability of drugs in mixtures simultaneously. Physical stability study has been carried out by visual inspection, pH measure and gravimetry to control evaporation. The results shown in this paper represent the first evidence of the physico-chemical stability of both ternary mixtures used in clinical practice at different conditions of storage. The ternary mixtures of FDG in 100 and 250 ml of 0.9 g/dl NaCl are physico-chemical stable for 15 days at room temperature and refrigerated and exposed to and protected from light; mixtures in 50 ml are physico-chemical stable for 6 days. The ternary mixtures of FDO in 50, 100 and 250 ml of 0.9 g/dl NaCl are physico-chemical stable for 15 days at both conditions of temperature and light.

ChemInform Abstract: Chemical Drug Stability in Lipids, Modified Lipids, and Polyethylene Oxide‐Containing Formulations

AbstractReview: 44 refs.

Chemical stability of drugs: Influence of light and temperature on montelukast stability in solution

In this paper, influence of temperature and light on stability of montelukast in solutions (standard substance, chewable tablets and film coated tablets) which were prepared during routine analysis of related substances was investigated. The content of montelukast and degradation products was determined by HPLC method at defined time intervals (influence of temperature was tested at the beginning, after 24 hours, and after 48 hours, and influence of light was tested at the beginning of the experiment and after 12 hours). Stability of montelukast in tested solutions under influence of temperature was acceptable. The content of montelukast ranged from 98 % to100 %, which meets the pharmacopoeia requirements and specifications. Individual and total impurities were within acceptable limits. Presence of photosensitive functional groups in structure of montelukast led to significant photodegradation. Individual and total impurities in samples which were under influence of light were above acceptable limits. Photodegradation occured during first 12 hours. Content of MOK-3 sulphoxide and unknown impurity on RRT 0.76 was above limits in all examined samples. Over a period of 12 h the content of those impurities grew 8-40 fold compared to time zero values.

Chemical Drug Stability in Lipids, Modified Lipids, and Polyethylene Oxide-Containing Formulations

To critique the stability complications seen in formulating poorly water-soluble, problematic drugs in lipids, modified lipids, and polyethylene oxide solvents and surfactants in hard and soft gelatin capsules as well as some parenterals, a literature search was performed and personal experiences, and those of colleagues, collated. The literature is replete with examples of molecules undergoing rapid oxidative degradation in the presence of polyethylene oxide based solvents and surfactants as well as in the presence of unsaturated lipids. More recently appreciated is instability caused by the reaction of amine and amide drugs, with formaldehyde, formic acid found in many of these solvents as impurities and other degradation byproducts of the solvents themselves. One would expect acylation and transacylation reactions to be more common than reported but the literature has some good examples. An added complexity is occasionally seen with the use of hard and soft gelatin capsules with these solvents. The chemical stability of drugs in liquid and semi-solid formulations in the presence of lipids, modified lipids, and polyoxyethylene oxide-based solvents and surfactants can be complex, further exacerbated by the use of gelatin capsules, and can lead to a plethora of degradation pathways often not seen when the same drugs are formulated in solid dosage forms.

Polymer Nanoassemblies for Cancer Treatment and Imaging

Amphiphilic polymers represented by block copolymers self-assemble into well-defined nanostructures capable of incorporating therapeutics. Polymer nanoassemblies currently developed for cancer treatment and imaging are reviewed in this article. Particular attention is paid to three representative polymer nanoassemblies: polymer micelles, polymer micellar aggregates and polymer vesicles. Rationales, design and performance of these polymer nanoassemblies are addressed, focusing on increasing the solubility and chemical stability of drugs. Also discussed are polymer nanoassembly formation, the distribution of polymer materials in the human body and applications of polymer nanoassemblies for combined therapy and imaging of cancer. Updates on tumor-targeting approaches, based on preclinical and clinical results are provided, as well as solutions for current issues that drug-delivery systems have, such as in vivo stability, tissue penetration and therapeutic efficacy. These are discussed to provide insights on the future development of more effective polymer nanoassemblies for the delivery of therapeutics in the body.

Interpenetrating network hydrogel beads of carboxymethylcellulose and egg albumin for controlled release of lipid lowering drug

Novel interpenetrating network hydrogel beads of sodium carboxymethylcellulose and egg albumin loaded with a lipid lowering drug, simvastatin, were prepared by ionotropic gelation and covalent cross-linking method. The IPN beads were characterized by differential scanning colorimetric analysis, X-ray diffractometry to understand the crystalline nature of the drug after entrapment into IPN matrix. Fourier transform infrared spectroscopy was used to find the chemical stability of drug in the polymer matrix and scanning electron microscopy was performed to study the surface morphology. The ionically cross-linked beads were capable of releasing drug up to 7 h, whereas the drug release was extended up to 12 h in case of dual cross-linked beads. The beads which were prepared with higher concentration of glutaraldehyde released the drug more slowly. The release data were fitted to an empirical equation to determine the transport mechanism, which indicated the non-Fickian trend for drug transport.

Effects of microwave on drug release properties of matrices of pectin

The influence of microwave irradiation on the drug release properties of pectinate and pectinate–chitosonium beads was investigated. The beads were prepared with the highest possible concentration of polymer by an extrusion method. Sodium diclofenac was selected as a model water-soluble drug. The beads were subjected to microwave irradiation at 80 W for 5, 10, 21 and 40 min. The profiles of drug dissolution, drug content, drug stability, drug–polymer interaction and polymer–polymer interaction were determined by dissolution testing, drug content assay, differential scanning calorimetry (DSC) and Fourier transform infra-red spectroscopy (FTIR). The chemical stability of drug in beads was unaffected by the microwave irradiation. The drug release property of pectinate beads was mainly governed by the extent of polymer interaction in matrix. Treatment of pectinate beads by microwave led to an increase in the extent and rate of drug released owing to reduced pectin–pectin interaction via C O of COOH and/or COOCH 3 of the polymer. The extent of drug released from the pectinate beads could not be reduced merely through the coacervation of pectinate matrix with chitosan. Treatment of pectinate–chitosonium beads by microwave was essential to reduce the rate and extent of drug released from the matrix, following an increase in drug–polymer and polymer–polymer interaction in beads. Treatment of chitosonium beads by microwave at 80 W for 5 min reduced the rate and extent of drug released from the matrix. Nonetheless, the degree of reduction in the extent of drug released from the chitosonium beads was lower than that of the pectinate–chitosonium matrix and the release of drug from the chitosonium samples was not markedly retarded through the treatment of beads by microwave for a period of duration longer than 5 min. The findings indicated that both pectin and chitosan were needed in the formulation of a controlled-release matrix using the microwave technology.

Physico-Chemical Characterization and Stability Study of Glassy Simvastatin

The objective of the present study was to investigate the glass forming capability of a model drug simvastatin. The glassy material produced by melt quench technique was subjected to physico-chemical characterization and subsequent stability and enthalpy relaxation study. The chemical stability of drug during preparation of glass was tested by High Performance Liquid Chromatography (HPLC) and Infrared (IR) spectroscopy. The presence of amorphous form was confirmed by DSC and XRPD. Surprisingly, glassy simvastatin was almost stable throughout the period of stability, inspite of its Tg being relatively low. The stability and very low enthalpy recovery of glassy simvastatin perhaps could be attributed to strong inter-molecular hydrogen bonding.

Stability studies on steroidal drug/β-cyclodextrin kneaded systems

6-Methylenandrosta-1,4-diene-3,17-dione (FCE24304), an aromatase inhibitor, is characterised not only by poor solubility in aqueous media and slow dissolution rate, but also by low chemical stability due to possessing conjugate double bonds. Several approaches have already been evaluated for improving both the biopharmaceutical properties and chemical stability of drugs in a particular way by the use of β-cyclodextrin. An accelerated short-term stability study on FCE24304β-cyclodextrin kneaded systems, prepared using two different molar ratios, was carried out and the systems evaluated by HPLC, DSC and X-ray difiractometry techniques and correlated with dissolution rate behaviour. A tablet formulation with a 1:2 molar ratio of the FCE24304/β-cyclodextrin complex is now under development.

ChemInform Abstract: The Molecular Basis of Moisture Effects on the Physical and Chemical Stability of Drugs in the Solid State

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Effect of storage on nitrofurantoin solid dosage forms

Storage under adverse conditions of temperature and humidity is not uncommon in many parts of the world. Packages used for the dispensing of medications are often less than adequate. These conditions may adversely affect the quality of pharmaceutical preparations (Gouda et al., 1980; York, 1977). While changes in the chemical stability of drugs in their dosage forms dre usually easily detected, changes in biopharmaceutical properties may pass unnoticed. Nitrofurantoin, a urinary tract antibacterial drug, has a potential for bioavailability problems. Formulation factors, mainly particle size, affect dissolution rate, bioavailability in humans and incidence of side-effects (Cadwallader et al., 1975). The USP XX monograph for nitrofurantoin tablets requires not less than 25% of the labeled amount of drug to dissolve in 60 min in a pH 7.2 phosphate buffer. The objectives of the present study are to determine the effect of storage on the dissolution of nitrofurantoin tablets and capsules and to assess any bioavailability changes associated with storage. Two brands of nitrofurantoin capsules containing macroor microcrystals and a tablet were stored in original blister packs, in child-proof vials and in plastic bags. The storage conditions adopted were 40°C/79W relative humidity (R.H.), 25”C/79% R.H. and 40°C/31W R.H. Samples were taken at various time intervals and the drug content, weight variation and dissolution at 3j”C in a pH 7.2 phosphate buffer (USP XX) were determined. A limited bioavailability study based on determination of urinary excretion of unchanged drug was also carried out. Administration of stored (in plastic bags for 10 weeks at 40°C/79% R.H.) and unstored capsules under non-fasting conditions (Bates et al., 1974) to two healthy volunteers was performed in a cross-over design. W rine samples were collected at various time intervals and analyzed for nitrofurantoin (Conklin and tlollifield, 1965).