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

Development and characterisation of semi-crystalline composite granules: the effect of particle chemistry and the electrostatic charging

This study investigated the surface of semi-crystalline composite granules produced via a novel mechano-chemical process and assessed the effect of electrostatic charging. Ibuprofen (IBU), a model drug with low solubility and known associated processing challenges was loaded in composite granules to improve its processibility and dissolution rates. Synthetic amorphous mesoporous magnesium alumina metasilicate (MAS) was co-processed with hydrophilic HPMC polymer in the presence of polyethylene glycol 2000 (PEG) and deionised water. The solid state analyses conducted by scanning electron microscopy (SEM), X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) revealed the existence of semi-crystalline IBU in the complex composite structures. Dynamic vapour sorption (DVS) study showed the water sorption and desorption profiles of the manufactured composite granules as well as the effect of water on the solid-state stability of IBU in various formulations. Advanced surface analysis conducted via energy dispersive X-ray (EDS) revealed homogenous distribution of the drug/excipients on the surface of the granules while atomic force microscopy (AFM) complemented the findings. The electrostatic charge analysis showed variable charge property which is affected by the size of the particles/granules. As expected, the in vitro dissolution study showed about 5 fold increase in the release rates of IBU compared to that of the bulk drug. The mechano-chemical processing has been demonstrated as an efficient technique to develop semi-crystalline composite granules with enhanced dissolution rates of water insoluble drugs

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

Evaluation of the surface chemistry and drug-polymer interaction of semi-crystalline micro-particles for the development of controlled release formulations

This research work explores the surface chemistry and drug-polymer interaction in the manufactured controlled release micro-particles. Isoniazid (INH) was used as a model anti-tubercular drug while Eudragit® S100 (S100), Eudragit® L100-55 based co-processed Acryl EZE (EZE) and Ethylcellulose ECN10 (ECN10) were used as polymeric carriers. INH containing micro-particles were prepared using a mini spray dryer B-290 (Buchi, Switzerland). The drug polymer ratios were optimized at 1:1 and 1:3 to evaluate the effect of polymers on the release of the drug from the micro-particles. Solid state characterization via SEM and particle size analysis of the manufactured micro-particles showed densely aggregated spherical particles with a mean diameter < 10 μm. The advanced surface analysis via EDS revealed a homogenous drug distribution on the spray dried micro-particles. The physico-chemical characterization carried out by using DSC and XRPD showed an increase in the amorphicity of the drug during the spray drying process while the chemical elemental analysis via XPS revealed a strong intermolecular interaction between the amine group of the drug and the carboxyl group of the polymers. As expected, the in vitro dissolution study showed a slow release pattern for the highly water soluble drug INH in acidic media (pH 1.2) for the first 2 h followed by a burst release upon changing the pH to 6.8. It was concluded that emerging spray drying processing can be used as a valuable tool to encapsulate drug for controlled release dosage forms by means of facilitating a possible drug/polymer interaction as outlined by novel XPS analysis

Can ion mobility mass spectrometry and density functional theory help elucidate protonation sites in 'small' molecules?

Ion mobility spectrometry-mass spectrometry (IMS-MS) offers an opportunity to combine measurements and/or calculations of the collision cross-sections and subsequent mass spectra with computational modelling in order to derive the three-dimensional structure of ions. IMS-MS has previously been reported to separate two components for the compound norfloxacin, explained by protonation on two different sites, enabling the separation of protonated isomers (protomers) using ion mobility with distinguishable tandem mass spectrometric (MS/MS) data. This study reveals further insights into the specific example of norfloxacin and wider implications for ion mobility mass spectrometry

Continuous manufacturing of high quality pharmaceutical cocrystals integrated with process analytical tools for in-line process control

A continuous manufacturing process for pharmaceutical indomethacin–saccharine cocrystals was achieved by extrusion processing with high throughput. Down-stream milling and blending of the extrudates was followed by feeding the formulated cocrystals in a capsule-filling machine. By applying a quality by design approach, the process was optimized and scaled up to produce 3000 capsules/h of pharmaceutical cocrystals. Process analytical tools such as near infrared reflectance and spatial filter velocimetry probes were coupled at various process stages for in-line monitoring and quality control. Further physicochemical characterization of extruded batches confirmed the manufacturing of high quality cocrystals. A fully integrated continuous process starting from raw materials to produce a finished product was assembled with only six unit operations and a small footprint. The study is a paradigm of continuous manufacturing of pharmaceutical cocrystals

Development and optimization of ketoconazole oral strips by means of continuous hot-melt extrusion processing

Objectives The aim of this study was to develop mucoadhesive oral strips using hot-melt extrusion as a continuous manufacturing process. Methods Powder blends of ketoconazole, a water-insoluble drug – either hydroxypropyl methylcellulose (HPMC) or soluplus (SOL), sorbitol (SRB) and magnesium aluminometasilicate (MAS) were extruded to manufacture thin strips with 0.5-mm thickness. The presence of the inorganic metasilicate facilitated smooth processing of the extruded strips as it worked as an absorbent directly impacting on the extensive mixing of the drug/excipients inside the extruder barrel. Key findings The use of MAS also favoured the rapid hydration, swelling and eventual disintegration of the strips. Differential scanning calorimetry and transmission X-ray diffraction analysis revealed the existence of the amorphous drug within the extruded strips. Scanning electron microscopy and energy dispersive X-ray undertaken on the formulations showed a homogeneous drug distribution within the extruded strips. Conclusion The strips produced via continuous hot-melt extrusion processing showed significantly faster release of ketoconazole compared to the bulk drug substance