Hydrophilic Matrices for Oral Control Drug Delivery

Oral controlled drug delivery has gathered tremendous attention over the years due to its many advantages over conventional dosage forms. Polymer-based matrices have become an integral part of the pharmaceutical industry. Hydrophilic matrices are capable of controlling the release of drug over an extended period of time. Hydrophilic polymers, especially the hydrophilic derivatives of cellulose ethers, are frequently used for these applications. Therefore, the objective of this review is to discuss the scientific and physicochemical aspects of these polymeric systems that can affect the drug release from such formulation

Tribo-electric Charging and Adhesion of Cellulose Ethers and their Mixtures with Flurbiprofen

The pervasiveness of tribo-electric charge during pharmaceutical processing can lead to the exacerbation of a range of problems including segregation, content heterogeneity and particle surface adhesion. The excipients, hydroxypropyl methylcellulose and methylcellulose, are often used in drug delivery systems and so it is important to understand the impact of associated factors on their charging and adhesion mechanisms, however, little work has been done. Such phenomena become more prominent when excipients are introduced to a powder mixture alongside the active pharmaceutical ingredient(s) (APIs) with inter- and intra-particulate interactions giving rise to electrification and surface adhesion of powder particles. The aim of this study was to understand the impact of material attributes (particle size, hydroxypropyl (Hpo) to methoxyl (Meo) ratio and molecular size) on the charging and adhesion characteristics of cellulose ethers. Furthermore, poorly compactible and highly electrostatically charged drug, flurbiprofen, was used to develop binary powder mixtures having different polymer to drug levels. Subsequently, a relationship between tribo-electric charging and surface adhesion was studied. Charge was induced on powder particles and measured using a custom built device based on a shaking concept consisting of a Faraday cup connected to electrometer. The diversity in physicochemical properties has shown a significant impact on the tribo-electric charging and adhesion behaviour of MC and HPMC. Moreover, the adhesion and electrostatic charge of the API was significantly reduced when MC and HPMC were incorporated. Moreover, tribo-electric charging shows a linear relationship (R2= 0.81-0.98) with particle surface adhesion, however, other factors were also involved. It is anticipated that such reduction in charge and particle surface adhesion would improve flow and compaction properties during processing

Release kinetics, compaction and electrostatic properties of hydrophilic matrices

This thesis illustrates the behaviour of cellulose ethers during powder processing, compaction and drug release, as these are frequently employed in the fabrication of compressed hydrophilic matrices. The handling operations can give rise to the electrification of powder particles, which can affect the end product‘s quality. Controlling the parameters which can dictate the quality of compressed matrices is an ambition inherent in the development of pharmaceutical formulations. Thus, the aims and objectives of this thesis were to firstly study the electrostatic, surface adhesion, dissolution and compaction properties of plain polymers and model drugs. Secondly, binary mixtures of fixed drug to polymer ratios were made in order to investigate the effect of polymer concentration and physico-chemical attributes (particle size, chemistry and viscosity) on the tribo-electric charging, surface adhesion (SA), swelling, erosion, drug release kinetics and compaction properties of model drugs. It can be discerned that the both drugs charged negatively, whereas the methylcellulose (MC) and hydroxypropyl methylcellulose (HPMC) particles charged positively. The physico-chemical properties associated with MC and HPMC, such as particle size, chemical heterogeneity and molecular size of cellulose ethers all have a significant effect on charging and adhesion behaviour of plain MC and HPMC particles. Moreover, the concentration, particle size, chemical heterogeneity and molecular size of MC/HPMC all significantly affect the charging and SA propensity of the model drugs studied. The swelling and dissolution results confirm that the extent and rate of swelling, swelling exponent, dissolution rate and drug release kinetic parameters were affected by physico-chemical attributes (concentration, particle size, substitution and viscosity) of MC/HPMC and drug solubility. The mechanism of swelling and drug release was found to be anomalous. However, it inclined towards more diffusion-oriented swelling/drug release with higher MC/HPMC levels, viscosity, Hpo/Meo substitution ratios, drug solubility but smaller MC/MC particle size. The matrix erosion results obtained from newly developed phenol-sulphuric acid assay (PSA) method confirmed that the solubility of the drug, and levels of HPMC in a particular matrix tablet, significantly affect the matrix erosion rate and the results were similar to those determined using the much more labour-intensive gravimetric method. Moreover, the combination of conventional UV drug analysis technique and PSA assay can be used to simultaneously quantify the matrix erosion, polymer dissolution and drug release kinetics in a single set of experiments avoiding the need for separate studies. The compaction results confirmed that the FBP has poor compaction as compare to THP. The particle size, substitution ratios and molecular size of MC/HPMC affect the compaction and consolidation behaviour of plain MC/HPMC compacts. Furthermore, it can be noticed that the concentration and physico-chemical attributes (particle size, chemistry and molecular size) of MC/HPMC have a significant influence on the densification and consolidation process of hydrophilic matrices. In summary, the information obtained can be used in the future to develop and adopt strategies for development and further optimization of compressed hydrophilic matrices

Nasal Drug Delivery Systems: An Overview

Since ancient times, drugs have been administered via the nasal route for therapeutic and recreational purposes. The interest in, and importance, of the systemic effects of drugs administered through the nasal route, have expanded over recent decades. Intra-nasal administration of drugs offers an interesting alternative for achieving systemic therapeutic effects of drugs that are comparable to the parenteral route, which can be inconvenient at times or oral administration, which can result in unacceptably low drug bioavailability. So, it is important to understand the potential and limitations of various nasal drug delivery systems. Therefore, the aim of this review article is to discuss the various pharmaceutical dosage forms that have the potential to be utilised for local or systemic drug administration. It is intuitively expected that this review will help to understand and further to develop suitable intra-nasal formulations to achieve specific therapeutic objectives

Starch-free grewia gum matrices: Compaction, swelling, erosion and drug release behaviour

Polysaccharides are suitable for application as hydrophilic matrices because of their ability to hydrate and swell upon contact with fluids, forming a gel layer which controls drug release. When extracted from plants, polysaccharides often contain significant quantities of starch that impacts upon their functional properties. This study aimed to evaluate differences in swelling, erosion and drug release from matrix tablets prepared from grewia gum (GG) and starch-free grewia gum (GDS) extracted from the stems of Grewia mollis. HPMC was used as a control polymer with theophylline as a model drug. Swelling, erosion, and in-vitro release were performed in deionized water, pH1.2 and pH6.8 media. The Vergnaud and Krosmeyer-Peppas model were used for swelling and drug release kinetics, respectively. However, linear regression technique was used to determine the erosion rate. GDS compacts were significantly harder than the native GG and HPMC compacts. GDS matrices exhibited the fastest erosion and drug release in deionised water and phosphate buffer compared with the GG and HPMC. At pH1.2, GDS exhibited greater swelling than erosion, and drug release was similar to GG and HPMC. This highlights the potential of GDS as a matrix for controlled release similar to HPMC and GG at pH1.2 but with a more rapid release at pH6.8. GDS may have wider application in reinforcing compacts with relatively low mechanical strengt

Physicochemical characterization of polysaccharides extracted from sesame leaves: a potential matrix for sustained release tablets

Purpose In the developing world the pharmaceutical sector depends heavily on imported raw materials which elevate the cost of medicines beyond the reach of the majority of the local population; despite often being rich in renewable sources which could be used as excipients. In this study we have extracted and characterised a largely undeveloped polysaccharide, sesamum gum, with a view to application as an alternative pharmaceutical excipient. Methods Polysaccharide from the leaves of Sesamum indicum was extracted by maceration in distilled water followed by precipitation in absolute ethanol. The material was oven dried and milled to a particle size of 250 m. The resulting material was characterized using X-ray diffractometry (XRD), Fourier transform infra-red spectroscopy, differential scanning calorimetry and thermogravimetric analysis. The total carbohydrate content, protein content and intrinsic viscosity of the extracted gum were determined according to standard protocols. Constituent sugar analysis of the material was determined by high performance anion exchange chromatography after hydrolysis of the samples using 2M trifluoroacetic acid for 3 hours. Compaction studies were carried out using a Testometric materials testing machine and data analysed by Heckel analysis. Results The polysaccharide gum had a total carbohydrate content of 98.1% and protein content of 1.7%. XRD spectra were typical of an amorphous material with a maximum decomposition temperature of 266.7 °C. Intrinsic viscosity was determined to be approximately 3.31 and 4.40 dl/g in 0.1 M NaCl and deionized water respectively. Dispersions of the polysaccharide are viscoelastic and exhibit shear-thinning behaviour. The polysaccharide contains fucose (0.1%), rhamnose (1.1%), arabinose (2.8%), galactose (48.9%), glucose (2.7%), mannose (6.8%) and xylose (33.6%) as neutral sugars, and glucuronic acid (3.0%) and galacturonic acid (1.1%) as acid sugars. Heckel analysis indicates that sesamum consolidates plastically having mean yield pressure of 131.45 MPa. Conclusion Sesamum polysaccharide is typically amorphous with a low content of uronic acids. Results suggest it is a thermally stable, high molecular weight polymer which exhibits shear-thinning behaviour in the hydrated form. The polymer in the dry state is a highly compactable material which has the potential to be exploited as a matrix former in sustained release tablets

Hydration and Erosion Properties of Cellulose Ethers

Purpose Hydrophilic derivatives of cellulose ethers (methylcellulose, MC and hypromellose, HPMC) are employed in controlled drug delivery polymeric devices because of their potential to control drug release profiles. Mechanistically, hydration and erosion (dissolution) of polymeric chains are the fundamental parameters that determine the rate of drug release. The aim of this work was to study the hydration and erosion properties of MC and HPMC, applying the Vergnaud model and a phenol-sulphuric acid assay respectively. The impact of different physicochemical properties (particle size, substitution levels and molecular size) was also investigated. Methods A gravimetrical method was employed for studying swelling of MC and HPMC matrices using pH 7.2 phosphate buffer (20 ml) as a hydration medium and hydration kinetics were analysed using Vergnaud model. The erosion of matrices was studied using USP I apparatus (pH 7.2 phosphate buffer, 900 ml) at 37°C and 100 rpm. The amount of dissolved polymer was quantified by application of a phenol-sulphuric acid (PSA) assay. Results The increased polymer molecular weight and substitution level of hydroxypropoxy groups led to higher swelling rate ranges between 41.01 to 89.74 (% h-1) but a lower degree of erosion, which declined from 0.020 to 0.005 (% min-1). This was also true of reduced particle sizes, regardless of MC and HPMC grades. The mechanism of hydration for all the matrices was observed to be diffusion controlled as values of swelling exponent (n) were < 0.5 in all cases. Conclusion From the current study it can be inferred all these matrices underwent diffusion controlled hydration. The particle size, substitution levels and increasing molecular weight demonstrated a clear influence on swelling and erosion rates. The PSA assay was successfully applied to study polymer erosion kinetics from cellulose ethers with varied physicochemical properties