Powder Compaction: Compression Properties of Cellulose Ethers

Effective development of matrix tablets requires a comprehensive understanding of different raw material attributes and their impact on process parameters. Cellulose ethers (CE) are the most commonly used pharmaceutical excipients in the fabrication of hydrophilic matrices. The innate good compression and binding properties of CE enable matrices to be prepared using economical direct compression (DC) techniques. However, DC is sensitive to raw material attributes, thus, impacting the compaction process. This article critically reviews prior knowledge on the mechanism of powder compaction and the compression properties of cellulose ethers, giving timely insight into new developments in this field

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

Uusi menetelmä aineiden mekaanisten ominaisuuksien mittaamiseksi

In tablet compression the objective is to obtain a durable tablet. The main deformation mechanism of substance affects how good tablet is obtained. The pharmaceutical powders is often divided into two categories with respect to their principal deformation mechanism: plastic and fragmented. Good tablet formulation requires its components to deform with both of these mechanisms. It is possible to examine in many ways, whether material is plastic or fragmented. These include force-time graphs and indentation methods, as well as different compression equations such Heckel equation. Examination and identification of the deformation mechanisms is important in order to design a formulation which provides the most durable tablet. The aim of experimental work in this study was to test the new compression device and method, and to compare the results of the device shown in the earlier literature results. Comparison with previous research, new in this study was compression rate and without a motor acting compaction system. In this study, there was two compression method developed, dynamic and static. Data from a dynamic method were analysed by time-travel - and force-displacement -curves. Results were parameterized, and on the basis of these parameters the behaviour of various materials was evaluated and compared to the earlier literature. Relaxation study was also performed in this research. The results of these measurements were analysed with the parameterized function fit, after which the results were compared with earlier results presented in the literature. The results of this work in dynamic measurements are cosistent with the research results received earlier. In terms of almost all parameters investigated, substances were divided into two groups in the same way as in the previous literature on the basis of the main deformation mechanism. The results obtained in static measurements, however, were quite inconsistent with previous research. Based on the results it can be stated that the method makes it possible to get consistent results with the literature. However, the method still requires development, and possible error sources and the choice of analytical method should pay special attention.Tabletin puristuksessa tavoitteena on saada jauheesta tiivis ja kestävä tabletti. Aineen pääasiallinen muotoutumismekanismi vaikuttaa siihen kuinka hyvä tabletti jauheesta saadaan. Farmaseuttiset jauheet jaetaan usein kahteen luokkaan niiden pääasiallisen muotoutumismekanismin suhteen: plastiseen ja fragmentoituvaan. Hyvä tablettiformulaatio vaatii kummallakin mekanismilla muotoutuvia komponentteja. Näitä muodonmuutosmekanismeja on mahdollista tutkia aineesta monella tavalla. Tällaisia ovat mm. voima-aika -kuvaajat ja indentaatiomenetelmät, sekä erilaiset puristusta kuvaavat yhtälöt, kuten Heckelin yhtälö. Muodonmuutosmekanismien tutkiminen ja tunnistaminen on tärkeää, jotta voidaan suunnitella formulaatio josta saadaan mahdollisimman kestävä tabletti. Tässä työssä kokeellisen osan tavoitteena oli testata uutta laitetta ja menetelmää, ja verrata laitteella saatuja tuloksia aiemmin kirjallisuudessa esitettyihin tuloksiin. Työssä testatussa menetelmässä uutta verrattuna aiempiin tutkimukseen oli käytetty puristusnopeus ja ilman moottoria toimiva puristussysteemi. Tutkimuksessa kehitettiin kaksi puristusmenetelmää, dynaaminen ja staattinen. Dynaamisella menetelmällä saatuja mittaustuloksia analysoitiin aika-matka - ja voima-matka -kuvaajien avulla. Niiden avulla parametroitiin mittaustulokset, ja näiden parametrien perusteella arvioitiin eri aineiden käyttäytymistä ja verrattiin sitä aiemmin kirjallisuudessa. Tässä tutkimuksessa suoritettiin myös relaksaatiomittauksia. Näiden mittausten tulokset parametroitiin funktiosovituksen avulla, jonka jälkeen tuloksia verrattiin aiemmin kirjallisuudessa esitettyihin tuloksiin. Tässä työssä dynaamisissa mittauksissa saadut tulokset ovat linjassa aiemmin saatujen tutkimustulosten kanssa. Lähes kaikkien tutkittujen parametrien suhteen aineet jakautuivat kahteen ryhmään samalla tavoin, kuin aiemmassa kirjallisuudessa pääasiallinen muotoutumismekanismin perusteella. Staattisessa mittauksessa saadut tulokset sen sijaan olivat melko ristiriitaisia aiemman tutkimustiedon kanssa. Tulosten perusteella voidaan kuitenkin todeta, että menetelmällä on mahdollista saada kirjallisuuden kanssa linjassa olevia tuloksia. Menetelmä vaatii kuitenkin vielä kehitystä, ja mahdollisiin virhelähteisiin ja tulosanalyysimenetelmän valintaan tulisi kiinnittää jatkossa erityistä huomiota

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

Improving powder tableting performance through materials engineering

University of Minnesota Ph.D. dissertation. 2015. Major: Pharmaceutics. Advisor: Changquan Sun. 1 computer file (PDF); 322 pages.Adequate mechanical strength is a critical requirement to the successful development of a tablet product. Before tablet compression, powders are often engineered by various processes including wet granulation and surface coating, which may improve or adversely affect the powder tableting performance. Such effects, commonly, result from a change in either particle mechanical properties or particulate (size, shape) properties. In this work, tableting performance is interpreted based on the qualitative bonding-area and bonding-strength (BABS) model. The tabletability of the microcrystalline cellulose (MCC) granules deteriorates rapidly with increasing amount of granulating water and eventually leads to over-granulation at high water level. Granule surface smoothing, size enlargement, granule densification and shape rounding are the dominant factors leading to the tabletability reduction of plastic MCC. Incorporation of increasing amounts of brittle excipients, such as lactose or dibasic calcium phosphate reduces the rate of tabletability reduction by promoting more granule fragmentation, introducing more surface area available for bonding. When a sufficient amount of brittle excipients is used, the over-granulation phenomenon can be eliminated. Surface coating of incompressible MCC pellets with highly bonding polymer leads to sufficient surface deformation and adhesion to enable direct compression of the pellets into tablets of adequate mechanical strength. This improvement is enhanced by the presence of moisture, which plasticizes the polymer to allow the development of a larger bonding area between coated pellets. The relationship between mechanical properties and tableting behavior is systematically investigated in polymeric composites using celecoxib-polyvinylpyrrolidone vinyl acetate solid dispersions. Mechanical properties such as indentation hardness of the solid dispersions were measured using nanoindentation. Incorporation of celecoxib up to 60% by weight hardens the polymers, which reduces bonding area but increases bonding strength. On the other hand, moisture softens the solid dispersions and facilitates deformation under pressure to improve tablet mechanical strength. In summary, insights into the deteriorated tabletability of wet granulated powders have been developed and strategies for improving tabletability have been demonstrated. Also, the relationship between particle mechanical properties and tableting performance has been examined using solid dispersions. The BABS model has been further developed to enable its widespread application in interpreting complex tableting behavior