Formulation development of a carrageenan based delivery system for buccal drug delivery using ibuprofen as a model drug

Solvent cast films are used as oral strips with potential to adhere to the mucosal surface, hydrate and deliver drugs across the buccal membrane. The objective of this study was the formulation development of bioadhesive films with optimum drug loading for buccal delivery. Films prepared from κ-carrageenan, poloxamer and polyethylene glycol or glycerol, were loaded with ibuprofen as a model water insoluble drug. The films were characterized using texture analysis (TA), hot stage microscopy (HSM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), x-ray powder diffraction (XRPD), high performance liquid chromatography (HPLC) and in vitro drug dissolution. Optimized films were obtained from aqueous gels containing 2.5% w/w κ-carrageenan 911, 4% w/w poloxamer 407 and polyethylene glycol (PEG) 600 [5.5% w/w (non-drug loaded) and 6.5% w/w (drug loaded)]. A maximum of 0.8% w/w ibuprofen could be incorporated into the gels to obtain films with optimum characteristics. Texture analysis confirmed that optimum film flexibility was achieved from 5.5% w/w and 6.5% (w/w) of PEG 600 for blank films and ibuprofen loaded films respectively. TGA showed residual water content of the films as approximately 5%. DSC revealed a Tg for ibuprofen at −53.87°C, a unified Tm for PEG 600/poloxamer mixture at 32.74°C and the existence of ibuprofen in amorphous form, and confirmed by XRPD. Drug dissolution at a pH simulating that of saliva showed that amorphous ibuprofen was released from the films at a faster rate than the pure crystalline drug. The results show successful design of a carrageenan and poloxamer based drug delivery system with potential for buccal drug delivery and showed the conversion of crystalline ibuprofen to the amorphous form during film formation

An Overview of Chitosan-Xanthan Gum Matrices as Controlled Release Drug Carriers

Naturally occurring polysaccharides and/or their chemically modified derivatives have been widely investigated in relation to their use as components of controlled release systems for drug delivery. The aforementioned is due, in part, to their distinct properties such as abundant availability and biocompatibility as well as environmental and economic advantages. Chitosan (CS) and xanthan gum (XG) based matrices have received growing scientific/pharmaceutical interest as oral controlled release drug carriers. Herein, recent advances spanning the last two decades in CS-XG based drug delivery systems are reviewed with the emphasis being on oral tablet formulations, due to their versatility as pharmaceutical dosage forms. The mechanism of interaction between CS and XG, by means of computational and experimental approaches, is scrutinized. Results obtained from the literature establish the possibility of fabricating a controlled release drug delivery system based on CS and XG matrices. This can be achieved by monitoring and manipulating the physiochemical properties of the two polymers as well as the experimental variables affecting their drug retardation efficiency, without the need to employ special equipment or sophisticated experimental techniques/methodologies

Thermal studies of L, D and β-alanine

α-Amino acids are generally studied by spectroscopic techniques, to determine their structure and distinguish between L and D forms (Caroline et al., 2009). Their study via thermal analysis is usually combined with other analytical techniques such as FT-IR, MS, HPLC, GC or NMR to identify the products of thermal decomposition (Kumar et al., 2006, Rodante and Marrosu, 1990). It is intriguing to ascertain whether thermal analytical techniques alone can provide useful information about amino acids, in terms of their physicochemical properties, and their techniques ability to distinguish between L and D forms

Bone mineral health is sensitively related to environmental cadmium exposure- experimental and human data

Exposure to cadmium (Cd) is recognised as one of the risk factors for osteoporosis, although critical exposure levels and exact mechanisms are still unknown. Here, we first confirmed that in male Wistar rats challenged orally with 6 different levels of Cd (0.3–10 mg/kg b.w.), over 28 days, there was a direct dose relationship to bone Cd concentration. Moreover, bone mineral content was significantly diminished by ∼15% (p < 0.0001) plateauing already at the lowest exposure level. For the other essential bone elements zinc (Zn) loss was most marked. Having established the sensitive metrics (measures of Cd exposure), we then applied them to 20 randomly selected human femoral head bone samples from 16 independent subjects. Bone Cd concentration was inversely proportional to trabecular bone mineral density and mineral (calcium) content and Zn content of bone, but not the donor's age. Our findings, through direct bone analyses, support the emerging epidemiological view that bone health, adjudged by mineral density, is extremely sensitive to even background levels of environmental Cd. Importantly, however, our data also suggest that Cd may play an even greater role in compromised bone health than prior indirect estimates of exposure could reveal. Environmental Cd may be a substantially determining factor in osteoporosis and large cohort studies with direct bone analyses are now merited

Glassy state molecular mobility and its relationship to the physico-mechanical properties of plasticized hydroxypropyl methylcellulose (HPMC) films

Changes in tensile properties and the glass transition temperature (Tg) of plasticized polymer films are typically attributed to molecular mobility, often with no empirical data to support such an assertion. Herein solvent cast HPMC films containing varying amounts of PEG, as the plasticizer, were used to assess the dependence of tensile properties and the Tg on glassy state molecular mobility. Molecular mobility (molecular relaxation time and temperature) parameters were determined by Thermally Stimulated Current Spectroscopy (TSC). The tensile properties and Tg of the HPMC films were determined by texture analysis and DSC, respectively. Molecular mobilities detected by TSC were cooperative and occurred at temperatures (Tg’) well below (113 to 127 °C) the bulk Tg. The relaxation times (τ) were 71 ± 1, 46 ± 1, 42 ± 1, 36 ± 1 and 29 ± 1 s for HPMC films containing 0, 6, 8, 11 and 17 % (w/w) PEG, respectively. The Tg and glassy state molecular mobility were found to be intimately linked and demonstrated a linear dependence. While tensile strength was found to be linearly related to molecular relaxation time, tensile elongation and elastic modulus exhibited a non-linear dependence on molecular mobility. The data presented in this work demonstrates the complex nature of the relationship between plasticizer content, molecular mobility, Tg and tensile properties for plasticized polymeric films. It highlights the fact that the dependence of the bulk physico-mechanical properties on glassy state molecular mobility, differ greatly. Therefore, empirical characterization of molecular mobility is important to fully understand and predict the thermo-mechanical behavior of plasticized polymer films. This work demonstrates the unique capability of TSC to provide key information relating to molecular mobility and its influence on the bulk properties of materials. Data generated using TSC could prove useful for stability and performance ranking, in addition to the ability to predict materials behavior using data generated at or below typical storage conditions in the pharmaceutical, food, and polymer industries

A direct compression matrix made from Xanthan gum and low molecular weight chitosan designed to improve compressibility in controlled release tablets

The subject of our research is the optimization of direct compression (DC), controlled release drug matrices comprising chitosan/xanthan gum. The foregoing is considered from two main perspectives; the use of low molecular weight chitosan (LCS) with xanthan gum (XG) and the determination of important attributes for direct compression of the mixtures of the two polymers. Powder flow, deformation behaviour, and work of compression parameters were used to characterize powder and tableting properties. Compression pressure and LCS content within the matrix were investigated for their influence on the crushing strength of the tablets produced. Response surface methodology (RSM) was applied to determine the optimum parameters required for DC of the matrices investigated. Results confirm the positive contribution of LCS in enhancing powder compressibility and crushing strength of the resultant compacts. Compactibility of the XG/LCS mixtures was found to be more sensitive to applied compression pressure than LCS content. LCS can be added at concentrations as low as 15% w/w to achieve hard compacts, as indicated by the RSM results. The introduction of the plasticity factor, using LCS, to the fragmenting material XG was the main reason for the high volume reduction and reduced porosity of the polymer mixture. Combinations of XG with other commonly utilized polymers in controlled release studies such as glucosamine, hydroxypropyl methylcellulose (HPMC), Na alginate (ALG), guar gum, lactose and high molecular weight (HMW) chitosan were also used; all the foregoing polymers failed to reduce the matrix porosity beyond a certain compression pressure. Application of the LCS/XG mixture, at its optimum composition, for the controlled release of two model drugs (metoprolol succinate and dyphylline) was examined. The XG/LCS matrix at 15% w/w LCS content was found to control the release of metoprolol succinate and dyphylline. The former preparation confirmed the strong influence of compression pressure on changing the drug release profile. The latter preparation showed the ability of XG/LCS to extend the drug release at a fixed rate for 12 h of dissolution time after which the release became slightly slower

Electrochemical Oxidation Assessment and Interaction of 2-aminoethanol and N, N-diethylethanamine Propagation in Acidic Medium

Electro�oxidation and inhibitor performance of copper specimens in 1 M hydrochloric acid solu� tion was investigated at room temperature by linear potentiodynamic polarization and gravimetric method in the presence of 2�aminoethanol (A) and N, N�diethylethanamine (D) as an inorganic inhibitor. The effect of the inhibitory concentration on the corrosion behavior of copper was studied over 288 hrs at 298°K. The inhibitory efficiency rise up to 96% for single induced and 98% for synergistic behavior. The adsorption mechanism characteristic was supported by SEM/EDX analysis and adsorption isotherm. From all indica� tion, the inhibitive efficiency of these compounds majorly depends on their molecular structure and concen� tration. The blocking effects of the surface interface were also explained on the basis of the inhibitor active action. 2�aminoethanol and N, N�diethylethanamine inhibits copper in 1 M HCl by strictly affecting both the anodic and cathodic sites. Portion of the surface covered calculated was also found to follow Langmuir adsorption isotherm

Consensus Recommendations for Clinical Outcome Assessments and Registry Development in Ataxias: Ataxia Global Initiative (AGI) Working Group Expert Guidance

To accelerate and facilitate clinical trials, the Ataxia Global Initiative (AGI) was established as a worldwide research platform for trial readiness in ataxias. One of AGI’s major goals is the harmonization and standardization of outcome assessments. Clinical outcome assessments (COAs) that describe or reflect how a patient feels or functions are indispensable for clinical trials, but similarly important for observational studies and in routine patient care. The AGI working group on COAs has defined a set of data including a graded catalog of COAs that are recommended as a standard for future assessment and sharing of clinical data and joint clinical studies. Two datasets were defined: a mandatory dataset (minimal dataset) that can ideally be obtained during a routine clinical consultation and a more demanding extended dataset that is useful for research purposes. In the future, the currently most widely used clinician-reported outcome measure (ClinRO) in ataxia, the scale for the assessment and rating of ataxia (SARA), should be developed into a generally accepted instrument that can be used in upcoming clinical trials. Furthermore, there is an urgent need (i) to obtain more data on ataxia-specific, patient-reported outcome measures (PROs), (ii) to demonstrate and optimize sensitivity to change of many COAs, and (iii) to establish methods and evidence of anchoring change in COAs in patient meaningfulness, e.g., by determining patient-derived minimally meaningful thresholds of change