Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS): a rapid test for enteric coating thickness and integrity of controlled release pellet formulations

There are no rapid dissolution based tests for determining coating thickness, integrity and drug concentration in controlled release pellets either during production or post-production. The manufacture of pellets requires several coating steps depending on the formulation. The sub-coating and enteric coating steps typically take up to six hours each followed by additional drying steps. Post production regulatory dissolution testing also takes up to six hours to determine if the batch can be released for commercial sale. The thickness of the enteric coating is a key factor that determines the release rate of the drug in the gastro-intestinal tract. Also, the amount of drug per unit mass decreases with increasing thickness of the enteric coating. In this study, the coating process is tracked from start to finish on an hourly basis by taking samples of pellets during production and testing those using BARDS (Broadband Acoustic Resonance Dissolution Spectroscopy). BARDS offers a rapid approach to characterising enteric coatings with measurements based on reproducible changes in the compressibility of a solvent due to the evolution of air during dissolution. This is monitored acoustically via associated changes in the frequency of induced acoustic resonances. A steady state acoustic lag time is associated with the disintegration of the enteric coatings in basic solution. This lag time is pH dependent and is indicative of the rate at which the coating layer dissolves. BARDS represents a possible future surrogate test for conventional USP dissolution testing as its data correlates directly with the thickness of the enteric coating, its integrity and also with the drug loading as validated by HPLC

Tracking yeast metabolism and the Crabtree effect in real time via CO2 production using Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS)

In this study, a new approach to measure metabolic activity of yeast via the Crabtree effect is described. BARDS is an analytical technique developed to aid powder and tablet characterisation by monitoring changes in the compressibility of a solvent during solute dissolution. It is a rapid and simple method which utilises a magnetic stir bar to mix added solute and induce the acoustic resonance of a vessel containing a fixed volume of solvent. In this study it is shown that initiation of fermentation in a yeast suspension, in aqueous buffer, is accompanied by reproducible changes in the frequency of induced acoustic resonance. These changes signify increased com-pressibility of the suspension due to CO2release by the yeast. A simple standardised BARDS protocol reveals yeast carbon source preferences and can generate quantitative kinetic data on carbon source metabolism which are characteristic of each yeast strain. The Crawford-Woods equation can be used to quantify total gaseous CO2produced by a given number of viable yeast when supplied with a fixed amount of carbon source. This allows for a value to be calculated for the amount of gaseous CO2produced by each yeast cell. The approach has the potential to transform the way in which yeast metabolism is tracked and potentially provide an orthogonal or surrogate method to determining viability, vitality and attenuation measurements in the future

Tracking cocrystallization of active pharmaceutical ingredients with Bbenzoic acid coformer using Broadband Acoustic resonance Dissolution Spectroscopy (BARDS)

This study investigates the use of Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS) as a detection method for the formation of cocrystals. BARDS is a novel approach that uses reproducible changes in the compressibility of a solvent as a sample dissolves to characterize and differentiate between materials and in this case cocrystallization. Two cocrystal systems with a 1:1 stoichiometry were examined, which used benzoic acid as a coformer with isonicotinamide and with theophylline. Cocrystals were prepared using dry and wet milling for periods from 1 to 40 min, and samples were analyzed using infrared spectroscopy, powder X-ray diffraction, and BARDS. Comparison of the BARDS data with the IR and PXRD data cross-validated the BARDS results. This study shows that BARDS can be used to rapidly assess the formation of these cocrystals at-line when milling or as a relatively low cost tool in preformulation product development. The data can also be used to gauge the unique entrained gas and gas volume generation of the cocrystal samples during dissolution and their dissolution kinetics

SCTP based Handover Mechanism for VoIP over IEEE 802.11b Wireless LAN with Heterogeneous Transmission Rates

Abstract — In this paper a transport layer handover mechanism for Voice over Internet Protocol (VoIP) in 802.11b using the Stream Control Transmission Protocol (SCTP) is proposed. The multi-homing feature of SCTP is used to allow connections to several 802.11b Access Points (AP’s). Probing packets that model VoIP encoded data at various transmission rates are used to obtain quality metrics from each of the available networks. Handover decisions are made based on the Mean Opinion Score (MOS) calculated from the ITU-T E-Model for voice quality assessment using the obtained measurements. The handover mechanism is shown to operate in 802.11b networks with heterogeneous transmission rates using multiple VoIP codecs. The results show a high correlation between the MOS predicted by the proposed mechanism and the MOS experienced by a VoIP call present in the network. Results verify the accurate operation of the scheme using multiple VoIP codecs at various transmission rates. A simulation showing an SCTP endpoint handover between heterogeneous transmission rate AP’s is presented. I

Evaluation of VoIP in a mobile environment using an end-to-end handoff mechanism

Abstract- In parallel with the growth of VoIP services, a large number of manufacturers have begun to develop multimode devices capable of connecting to multiple wireless access networks simultaneously. These multimode terminals have, in principle, the capability to support seamless handover between different radio access networks. One handover solution that utilises the IP diversity which these multimode devices can deliver is SIGMA. SIGMA is a promising end-to-end transport layer handover solution based on SCTP. The objective of this paper is to investigate if SIGMA is capable of providing seamless handover of VoIP calls without degradation in voice quality. To achieve this, we developed a Linux based testbed on which we implemented a VoIP client and server using SIGMA handoff. Each voice call uses the G.711 voice codec over RTP. PR-SCTP is used in place of the traditional UDP as the transport layer protocol. SIGMA based handover was used during full duplex voice calls between the client and server. The ITU-T E-Model has been used to calculate the voice quality during the handover. Results show that SIGMA can be used as a seamless handover mechanism for VoIP without any impact on voice quality. I