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Reproducing taste with a Norimaki Synthesizer

May 28, 2021

A Meiji University scientist has invented a method for digitally reproducing taste and flavour in the same just as we do for sound.

 

In the pharmaceutical industry, taste masking of bitter products intended for oral administration is often undertaken during the product formulation stage. The effectiveness of taste-masking methods

Since flavour is a dynamic sense that is influenced by formulation ingredient, effective assessment of taste masking requires actual sensory analysis to be done on the drug product in its final formulation. If the drug product is potent or cytotoxic then sensory analysis may not be possible.

An alternative approach is the use of an electronic tongue – which relies on converting molecular information in a product to generate a signature that can be related to certain qualities of the product, for example, acidic, bitter, salty, etc. nevertheless, the electronic tongue has disadvantages, notably, the need for a huge amount of previous measurements for calibration.

Thanks to Dr. Homei Miyashita, a professor in the aptly named Department of Frontier Media Science, Meiji University, Japan, formulators of drug products will be soon be able to accurately taste and profile their formulations without needing to sniff or taste any product.

Dr. Miyashita interest in food and taste goes a long way back to when he was a child. He has undertaken research on technology and the human senses while at Meiji University, culminating in the Norimaki Synthesizer.

You can read more about Dr. Miyashita’s device through this link: https://meiji.elsevierpure.com/en/publications/taste-display-that-reproduces-tastes-measured-by-a-taste-sensor

Sanofi and GSK initiate global Phase 3 clinical efficacy study of COVID-19 vaccine candidate

Sanofi and GSK initiate global Phase 3 clinical efficacy study of COVID-19 vaccine candidate

May 27, 2021
Today, Sanofi and GlaxoSmithKline plc (GSK) started enrolment in their Phase 3 clinical study to assess the safety, efficacy and immunogenicity of their adjuvanted recombinant-protein COVID-19 vaccine candidate. The global randomized, double-blind, placebo-controlled Phase 3 study will include more than 35,000 volunteers aged 18 and older from several countries, including sites in the US, Asia, Africa and Latin America.
Formulating

Hypromellose vs Polyethylene Oxide in the Formulation Matrix “Mini” Tablet Systems

May 26, 2021

Abstract

In this study, a novel ‘mini tablet’ matrix system was developed using hypromellose and polyethylene oxide to determine if it resolved the commonly faced issue of dose dumping in monolithic systems. Using theophylline as the model drug, dissolution profiles of the matrix mini tablets were obtained with the aid of a USP apparatus 1 and 4 The results indicate two-compartment mini-tablets exhibited slower drug-release as well as an absence of the initial rapid drug-release seen in one-compartment systems. Of the polymer combinations tested, polyethylene oxide (as the internal polymer) and hypromellose (as the external polymer) combination showed the highest potential for resisting dose-dumping when agitation was increased (showing only an increase of 4.1% in drug-release, in comparison to a 42.5% increase shown by a commercially theophylline product, Uniphyllin®), This study shows that the concept of a matrix mini tablet system is a promising option for preventing dose-dumping although further work is required to optimise the system.

 

Background to the study

The need for frequent oral administration in cases of chronic disease can deter patients’ compliance to medication. While prolonged drug-release formulations can reduce dosing frequency and support better patient compliance and outcomes (Augsburger and Hoag, 2008), the incorporation of large drug concentrations in a single dosage form poses a potential risk to patient’s a health should drug-release characteristics of the dosage form become affected, for instance, when the phenomenon of ‘dose-dumping’ occurs (Mayer and Hussain, 2005).

Dose dumping may be induced by several factors; the commonest ones being consumption of meals before ingestion of medication (Hendeles et al., 1985; Karim et al., 1985, Schmidt and Dalhoff, 2002). Hendeles et al.(1985) found that consumption of a breakfast of bacon and eggs prior to administration of theophylline sustained-release formulations induced dose-dumping. Dose dumping was attributed to exposure to the alkaline bile salts or pancreatic enzymes following postprandial gastric emptying.

Hydrophilic diffusion-based monolithic matrix systems are a popular sustained-release system due to their enhanced reliability, relatively cheap manufacturing cost and ease of formulation (Augsburger and Hoag, 2008). The drug is dispersed evenly in a polymer and upon contact with GI tract fluids, a gel-layer forms to serve as a barrier to fluid movement into and drug movement out of the system. Commonly used polymers for hydrophilic matrices include hypromellose, polyethylene oxide and methacrylic acid copolymers (Tiwari and Rajabi-Siahboomi, 2008, Appicella et al., 1993).

A flaw in the design of monolithic matrix systems is that when conditions promoting rapid drug-dissolution are encountered in vivo, a high proportion of the drug is immediately released into the gastrointestinal (GI) tract, potentially exposing the individual to a high dose (Hendeles et al., 1985). Previous attempts at modulating this initial burst of drug-release have been unsuccessful (Samuelov et al., 1979; Cobby, 1974; Conte (1993).

Novel ‘mini-tablet’ matrix systems, consisting of two-compartments, have been developed in an attempt to modulate drug release and to resolve the consequences of tablet rupture (De Brabander et al., 2000; Efentakis et al., 2000; Lopes et al., 2007). In this context, the two compartments are the mini-matrix tablet domain (internal) surrounded by a continuous polymer formulation (external). The containment of the drug within these internal polymer domains leads to an additional barrier separating the drug from GI fluid, thus preventing the immediate dumping of large quantities of drug. This is shown in figure 1 below.

Conceptualisation of the mini-tablet system. Grey area is the external polymer domain; the yellow area is the internal domain polymer and the blue dots represent the drugFigure 1: Conceptualisation of the mini-tablet system. Grey area is the external polymer domain; the yellow area is the internal domain polymer and the blue dots represent the drug

Objectives of the study

The objectives of the study were to determine the dissolution profiles of four different combinations of theophylline mini-tablets and to assess the suitability of PEO and HPMC as polymers for the internal and external domains of mini-tablets. Drug release profiles were investigated with the aid of the USP Apparatus 1 and 4 were used, with Hanks buffer at pH 7.4 used as the dissolution media. The vessels containing the media were sealed when possible throughout the investigation to prevent the escape of CO2.

Study Methodology

Materials

Theophylline anhydrous was purchased from Sigma Aldrich, UK, Hypromellose (Methocel™ K100M and Polyethylene Oxide (Polyox ™ WSR 1105) were kindly donated by Colorcon UK, Lactose anhydrous was gifted by Kerry Group, Dublin, Ireland, Colloidal Silica (HDK® N20 Pharma) was kindly provided by Wacker AG and Microcystalline Cellulose was purchased from Sigma ALdrich UK. The rest of the materials were technical grade materials purchased from a variety of vendors.

 

Methods

Preparation of Matrix ‘Mini Tablets’

Mini matrix tablets (total batch size of 400g) were prepared according to the scheme in table 1 and formulas in table 2 below.

 

Table 1:- The four combinations of the mini-tablet formulations evaluated

 

Internal mini-tablet polymer External polymer Tags
PEO HPMC P/H
PEO PEO P/P
HPMC Hypromellose H/H
HPMC PEO H/P

Table 2: Formulations used to produce mini-tablets

 

Ingredient % (w/W Quantity g (for 400g)
Theopylline 20.0 80
PEO/Hypromellose 20.0 80
MCC 15.0 60
Lactose 44.3 177.2
7-hydroxycoumarin 0.1 0.4
Magnesium Stearate 0.5 2
Colloidal silica 0.1 0.4

 

In each case, hypromellose or polyethylene oxide was blended with theophylline, microcrystalline cellulose and lactose for 5minutes. Magnesium stearate was then added and blending continued for a further 3 minutes. Finally, the 7-hydroxycumarin and colloidal silica were added and blending undertaken for a further 3 minutes.

All powder blends were assessed for flowability (Carr’s compressibility index and angle of repose). Tablet compression was undertaken on Riva Minipress Single Punch tablet press using 2 mm tooling. The obtained mini matrix tablets were then manually dosed into a 15 mm dies to which a portion of the appropriate external polymer blend had been added and compressed to create the mini matrix tablet system. Each system was designed to contain 50mg of theophylline.

Friability, hardness testing, and uniformity of weight of the macro tablets were performed using an ErwekaTA-120 friabilator and Erweka TBH-220D hardness machine.

 

Dissolution testing

USP Apparatus 1 dissolution testing at 100rpm

An Erweka DT 600A USP Apparatus 1 machine set to either 100rpm or 150 rpm (bath temperature 37°C) was used. 1L of Hanks buffer (pH 7.4) was placed in each vessel. At intervals of 0.5, 1, 2, 3, 4, 5, 6 and 26 hours, samples were withdrawn and absorbances taken using an Agilent UV spectrophotometer set at 268nm. The withdrawn aliquots were replaced with an equal amount of fresh dissolution media at the same temperature.

 

USP Apparatus 4: dissolution testing

A Sotax CE7 Smart USP Apparatus 4 was set to a temperature of 37°C and flow rate of 8 ml/min. One 5mm ruby bead was placed at the bottom of each of the 7 Dissotest cells and covered with 1mm glass beads up to one third of the cell. The tablets were placed into cells and Hanks buffer (pH 7.4) used as the test media. Readings were automatically taken at 30minute intervals for 15 hours. Measurements were performed in triplicate.

 

Results

Mini Tablets Characteristics

Lower compressibility and angle of repose values were obtained for the PEO powder compared with hypromellose suggesting that the PEO powder had better flow and tableting properties. Both powders produced tablets which had the weight and friability values consistent with current British Pharmacopoeia requirements (see table 3).

Table 3: Test results on macro tablets used to make the micro-domains

 

PEO Hypromellose
Powder flowability
Compressibility (%) 16.0 % 24.0 %
Angle of repose 36° 43°
Weight:
Mean 0.346g 0.349g
Standard deviation 0.002006 0.002102
Friability (%) 0.186 % 0.178%
Hardness:
Mean 96.1 ± 0.3 N 88.5 ± 0.4 N

Dissolution Tests

Drug release profile of the matrix systems are shown in Figure 2 to 4. Figure 2 and 3, which pertain to USP Apparatus 1 tests reveal faster drug-release in monolithic matrix tablets compared with the the two-compartment systems. The former also exhibit an initial rapid release of drug within the first 30 minutes. Increasing agitation (100 to 150 rpm) resulted in increase in drug-release. Systems formulated with PEO alone showed the fastest overall drug release profile. This was followed by commercial theophylline product.

The patterns of drug release for mini matrix tablet systems were clearly different from monolithic tablets. Moreover, there were differences between the different polymers with respect to what was added to the external versus internal phases. Finally, the two-compartment systems achieved more prolonged release and also avoided the initial spike in release, a result that is in agreement with what O’Connor (2011) reported.

Dissolution profiles of the 6 dosage forms using USP apparatus 1 at 100rpm

Figure 2: Dissolution profiles of the 6 dosage forms using USP apparatus 1 at 100rpm

Dissolution profiles of the 6 dosage forms using USP apparatus 1 at 150rpmFigure 3: Dissolution profiles of the 6 dosage forms using USP apparatus 1 at 150rpm

Cumulative percentage drug-release of 4 dosage forms using USP Apparatus 4Figure 4 shows the drug release profiles of the matrix systems as obtained from the USP Apparatus 4. The two-compartment matrix systems achieved more prolonged release while avoiding the initial spike in release. The PEO macro tablet had the fastest drug-release rate, followed initially by the commercial tablet. H/P, H/H and P/H systems, too, showed readings only from 1.5 hours. However P/H and H/H did not appear to release drug loads.

 

 

Figure 4: Cumulative percentage drug-release of 4 dosage forms using USP Apparatus 4

 

Discussion

The absence of the initial spike in drug-release with minitablets may be due to the lack of drug closer to dosage-form surface as the drug is contained within the internal domains. The distance presents a longer path for both the media and the drug travel, which slows down the diffusion and release of the drug substance. In monolithic matrices, if conditions present that promote drug to be released, there is an increased likelihood of reaching toxic-levels in these systems.

A direct comparison between P/P and the macro tablets highlight the difference in drug-release between one- and two-compartment models. Both used identical polymers yet had very different release profiles. The macro tablet released 50% of its dose in just 1.4 hours (at 100rpm) and 1.0 hours (at 150rpm) compared to the 9.5 hours (100rpm) and 5.9 hours (150rpm) of P/P, respectively representing a 7- and 6-fold increase in the time taken for the two-compartment model.

USP 4 data suggest the drug release characteristics of P/P system are unsuitable due to the rapid rate of drug release, which is even faster than the commercial tablets. This suggests that P/P systems are more prone to dose-dumping. H/H and P/H are also unsuitable as drug-release was extremely low and hence impractical for reaching the required therapeutic drug levels.

 

Effect of increasing agitation

The robustness of the formulations appears unrelated to whether the dosage forms were of a one- or two-compartment design. The greatest effect on drug release when rotation in USP 1 was increased from 100rpm to 150 rpm was seen on P/P where it showed to be 61% faster for the first 50% release of drug. H/P showed the second largest increase, followed by the commercial tablet at 42.5%, the macro tablet at 35.6%, and P/H at 4.1%. These results suggest presence of the internal domains alone is not enough to assume higher resistance to dose-dumping. Properties of the polymers within the dosage-form must also be considered. An investigation by Maggi et al. (2000) found the PEO gel-layer to be weaker and less-effective in preventing water-entry than the hypromellose gel-layer, resulting in an increased rate of gel-erosion and drug-release.

Figure 5 shows the result of an experiment where pure PEO and HPMC tablets were submerged in water. The presence of undissolved solids at 20 hours within the HPMC tablet system is indicative of hypromellose higher resistance to water entry into the tablet compared to PEO which showed no signs of undissolved polymer from 15hrs onwards. Additionally the greater diameter of the hypromellose tablet after 20 hours indicates the higher strength of its gel-layer.

 

Figure 5: Dissolution profile of tablets made of pure PEO (left) and HPMC (right) at 8hrs (top) 15hrs (middle) and 20hrs (bottom) (from from Maggi et al., 2000)

Figure 5: Dissolution profile of tablets made of pure PEO (left) and HPMC (right) at 8hrs (top) 15hrs (middle) and 20hrs (bottom) (from from Maggi et al., 2000)

 

Effect of internal and external domains on drug-release

H/P and P/H despite containing both hypromellose and PEO displayed very different drug-release and stability properties. This suggests that the influence of the polymer in the internal domain versus the external domain on drug-release is unequal. Performance at 100rpm of the two systems was selectively compared with P/P. H/P drug-release was only 24.6% less than P/P while P/H drug-release was 56.9% less, more effectively expressing the slower drug-releasing properties of HPMC. This suggests the polymer in the external domain influences drug-release more than the internal domain in two-compartment systems. These results coincide with observations made by Maggi et al. (2000) who found the external layers play the major role in controlling drug release.

 

Conclusions

PEO and Hypromellose, whether alone or in combination cannot achieve a suitably strong dosage form with good drug-release properties. P/H was the only formulation to show similar drug-release profiles for 100rpm and 150rpm. This may be an indication that this formulation is robust and is unlikely to dose dump. Further optimization is suggested, including the use of lower viscosity grades of hypromellose in the P/H formulation to tailor drug-release while maintaining resistance to erosion. Varying the external polymer as the internal domains appears to have less effect on the drug-release properties of the dosage-form and so should be kept constant.

 

References

Apicella, A. Cappello, B. Del Nobile, M. La Rotonda, M. Mensitieri, G. Nicholais, L. (1993). Poly (ethylene oxide) (PEO) and different molecular weight PEO blends monolithic devices for drug release. Biomaterials. 14 (2), 83-90.

Augsburger, L. and Hoag, S., 2008. Pharmaceutical Dosage Forms: Tablets. 3rd ed. Vol. 2: Rational Design and Formulation. Informa Healthcare USA, Inc.

De Brabander C, Vervaet C, Görtz JP, Remon JP, Berlo JA. Bioavailability of ibuprofen from matrix mini-tablets based on a mixture of starch and microcrystalline wax. Int J Pharm. 2000 Nov 4;208(1-2):81-6. doi: 10.1016/s0378-5173(00)00549-4. PMID: 11203270.

Cobby, J. Mayersohn, M. Walker, G. (1974). Influence of Shape Factors on Kinetics of Drug Release from Matrix Tablets. Journal of Pharmaceutical Sciences. 63 (5), 732-737.

Conte, U. Maggi, L. Colombo, P. La Manna, A. (1993). Multi-layered hydrophilic matrices as constant release devices ( GeomatrixTM Systems*). Journal of Controlled Release. 26, 39-47.

Efentakis M, Koutlis A, Vlachou M. Development and evaluation of oral multiple-unit and single-unit hydrophilic controlled-release systems. AAPS PharmSciTech. 2000;1(4):E34. Published 2000 Dec 1. doi:10.1208/pt010434

Hendeles, L. Weinberger, M. Milavetz, G. Hill, M. Vaughan, L. (1985). Food-induced “dose-dumping” from a once-a-day theophylline product as a cause of theophylline toxicity. Official publication of the American College of Chest Physicians. 87 (6), 758-765.

Karim, A. Burns, T. Wearley, L. Streicher, J. Palmer, M. (1985). Food-induced changes in theophylline absorption from controlled-release formulations. Part I. Substantial increased and decreased absorption with Uniphyl tablets and Theo-Dur Sprinkle. Clin Pharmacol Ther. 38, 77-83.

Lopes, C M, Lobo J M, Pinto J F, Costa P C. Compressed matrix core tablet as a quick/slow dual-component delivery system containing ibuprofen. AAPS PharmSciTech. 2007 Sep 21;8(3):E76. doi: 10.1208/pt0803076. PMID: 17915826; PMCID: PMC2750572.

Maggi, L. Bruni, R. Conte, U. (2000). High molecular weight polyethylene oxides (PEOs) as an alternative to HPMC in controlled release dosage forms. International Journal of Pharmaceutics. 195, 229-238.

Meyer, RJ. Hussain, AS. (2005). Mitigating the Risks of Ethanol Induced Dose Dumping from Oral Sustained/Controlled Release Dosage Forms.Center for Drug Evaluation and Research. 1, 1-4.

Samuelov, Y. Dunbrow, M. Friedman, D. (1979). Sustained release of drugs from Ethylcellulose-polyethylene glycol films and kinetics of drug release. Journal of Pharmaceutical Sciences. 68, 325-329.

Schmidt, L. Dalhoff, K. (2002). Food-Drug Interactions. Drugs. 62 (10), 1481-1502.

 

Hypromellose vs Polyethylene Oxide in the Formulation Matrix “Mini” Tablet Systems

B Hussain and J Simon

Pharmacentral Laboratory

Faculty of Science and Technology, University of Central Lancashire, Preston, PR1 2HE

“Natural”, “Naturally-Derived” and “Nature Identical” Excipients and Ingredients

May 26, 2021

A product’s label is a window in its soul, that’s what the product stands for, its benefits to its consumers. Claims such as ‘Natural’, ‘Fresh’ or ‘Artificial’ have a particular resonance with consumers, playing a key role in shaping purchase decisions and other behaviours.

Within the personal care and food/nutrition sectors, ‘natural’ status carries a lot of acclaim, as evidenced from the ever increasing sales of natural products or those with ‘natural’ claims. Natural skincare and nutrition brands have been growing at twice the rate of conventional products, a trend product developers and marketers seem to know very well about.

In the pharmaceutical sector, natural claims, while not carrying similar implications, are still important. Not only are there many excipients and active ingredients, including carbohydrate polymers, gums, surfactants, oils, flavours, alkaloids and antibiotics that are natural in origins or are naturally derived but consumers everywhere are increasingly seeking natural products due to their perception as being sustainable and friendly to the planet.

However, despite the widespread use of the term natural, the definitions of the terminology around natural, natural origin or artificial remains, to this day, in the regulatory equivalent of ‘no man’s land’. Regulators are as yet to provide official definitions or guidance on what is natural or not. Maybe because of the legal ambiguity, consumer groups and lawyers have been pushing for restrictions and/or legal redress on the uses of ‘natural’ and claims around ‘no artificial’ ingredients.

Consider xanthan gum, a gum that is widely used in the food, personal care and pharmaceutical products. Xanthan gum is produced by the bacterium, Xanthomonas campestris, which converts glucose into the gum. The process is a ‘natural’ fermentation process that occurs at its own pace without human intervention. Yet controversy as to whether xanthan gum is a natural product or not persists. Manufacturers using xanthan gum and attaching ‘natural’ claims to it have been a target of lawsuits challenging the ‘natural’ status of this material.

So what do ‘natural’ and ‘naturally derived’ mean?

This is by no means a definitive, legal guide. The FDA has not provided a regulatory definition of what natural entails when it comes to regulated products. The EU has guidelines on the use of ‘natural’ for nutritional claims (Regulation (EC) 1925/2006 but when it comes to other product groups, there still remains ambiguity. Therefore the use of the term ‘natural’ in advertising or labelling requires good judgment and legal counsel to avoid legal jeopardy.

Nevertheless, a material is considered ‘natural’ when it is ordinarily identified in nature, obtained and used in its natural, raw state after being extracted from the source. For example, Virgin Almond Oil Ph. Eur is the oil obtained by cold expression of the ripe seeds of Prunus dulcis. No further treatment (refining) or additives have been added.

The types of ‘permitted’ treatments include physical, enzymatic or microbiological processes on the plant or animal source material.

A material is referred to as ‘naturally derived’ or ‘natural origin’ when the natural source is treated to access other properties of the natural raw material; for example, getting natural fatty acids and natural fatty alcohols from a coconut.

By way of an example, natural fatty acids may require further processing in order to unlock or create certain aspects of the material’s properties beneficial for its function. Equally, potassium benzoate and lecithin require extraction and purification before they are in a state suitable for performance as preservatives or emulsifiers. Provided they are from plants, these materials can be classified as naturally derived.

A less encountered term is ‘nature identical’ which is typically used in relation to flavours. Nature identical flavours (vs artificial flavours) are flavours obtained by synthesis or isolated through chemical processes. The components are chemically and organoleptically identical to flavouring components present naturally present in nature. From a regulatory perspective, nature identical and artificial flavours are undistinguishable.

Standards and Certifications

A number of international standards and certification schemes on naturalness have been developed in recent times. They aim to help raw material suppliers and product manufacturers harmonise definitions on ingredient definitions and guide consumers. Although initially aimed at the cosmetics sector, the technical definitions and qualification schemes are equally applicable to food and pharmaceutical ingredients.

Below are three of the most important standards and schemes:

The COSMOS-standard

The COSMOS-standard was introduced in 2010. It aims to define and implement a standard for organic and natural cosmetics. The COSMOS standard includes guidelines on origin and approved processing procedures of the ingredients if they are to qualify as natural or organic. In addition to ingredients, the COSMOS standard also defines naturalness of the total product.

NaTrue Standard

The NaTrue Standard was developed by the NaTrue Scientific Committee Criteria and Label, an international non-profit organization. Its main focus is on cosmetics for which it seeks to clarify and promote natural and organic cosmetics globally. For ingredients, the NaTrue Standard differentiates between natural substances, nature-identical substances and derived natural substances, with a list of approved treatment processes. Furthermore, there are positive lists available for nature-identical substances, comprising pigments, minerals and preservatives.

 

ISO 16128

The ISO 16128 is a standard from the Geneva-based International Standard Organization. It aims to provide “Guidelines on technical definitions and criteria for natural and organic cosmetic ingredients and products”. ISO 16128 consists of two parts. Part 1 provides definitions for different ingredient categories. Part 2 describes the procedure on how to calculate the naturality of ingredients and the natural origin content of a cosmetic formulation, based on the amount of natural components in each raw material.

 

Conclusions

Even with the availability of standards and certifications the distinction between natural and unnatural is not always clear. In the absence of regulatory guidance, it falls to the formulator and marketer to make their own decision about what is natural and what is not, as there is no absolute definition, only opinions. This technical note will hopefully assist you in navigating the maze of natural and artificial ingredients.

Nearly half of COVID-19 patients left hospital in worse physical condition

May 25, 2021
Over a year after the novel coronavirus cemented its grip on the world, much of the conversation surrounding the disease remains simple: how many people died and how many survived?

But researchers at Michigan Medicine say a devastating side effect lurks, underreported, between those extremes – the loss of ability caused by the virus.

Formulating

A Fail-Safe Guide to Taste Masking Oral Products with Ion Exchange Resins

May 25, 2021

What are Ion Exchange Resins?

Ion Exchange Resins (IER) are synthetic pharmacopoeia grade water insoluble cross-linked polymers that contain a salt-forming group at regular positions on the polymer chain and have the capacity to exchange counter-ions in aqueous solution.

IERs were developed in the 1930s for water purifications applications. In the 1950s, they were introduced in the pharmaceutical industry as APIs and excipients. Currently, IERs are varyingly utilised as pharmaceutical excipients for controlling drug release agents (matrix tablets), solubility enhancement, increasing stability, taste masking and abuse deterrents.

Although there are many grades of IERs, only two materials currently meet official compendial requirements and are widely recommended for use in products. These are Polacrilin Potassium NF and Sodium Polystyrene Sulfonate USP-NF.

 

Selection and Grades of IERs

Polacrilin Potassium NF Sodium Polystyrene Sulfonate USP
Chemical Description Potassium salt of a cross-linked copolymer of methacrylic acid and divinylbenzene Sodium salt of a sulfonated copolymer of styrene and divinylbenzene
Physical Form White, fine or granular powder White, fine powder
Pharmacopoeia USP-NF USP-NF
Solubility Insoluble Insoluble
Hygroscopicity Hygroscopic Hygroscopic
Type Weak acid Strong acid
Functional Group -COO- -SO3–
Exchangeable Cation Potassium Sodium
pH Dependence Yes No
Commercial Grades AMBERLITE™ IRP88 (Dow)

KYRON T-134 (Corel Pharma)

 AMBERLITE™ IRP69 (Dow)

KYRON T-154 (Corel Pharma)

 

Advantages of IERs

  • IERs are highly versatile – they can be used in most oral drug delivery systems, including ODTs, tablets, chewable and effervescent tablet, capsules as well as dry syrups and liquid suspensions.
  • IERs can significantly improve safety and patient adherence by helping mask bitter tastes, improve bioavailability and reduce pill burden
  • IERs have a long history of use – spanning over 50 years of safety data.
  • IERs are simple to use – they do not require major changes to equipment or processes.

 

How to use IERs for Taste Masking

IERs provide an effective means to bind the bitter active principle onto an insoluble matrix via a simple ion exchange reaction. The reaction is a reversible, selective and stoichiometric exchange of ionic species that have similar charges.

The wet taste-masked complex can be used for suspension formulation directly. Alternatively, it can be dried and used in tablet, capsule or dry syrups.

The process of using IER for taste masking could not be any easier. There are two main ways to load the drug (API) on to the EIR: column method and batch method. The column method involves passing a highly concentrated solution of the API through a column of resin particles until equilibrium complexation is achieved. The batch process involves agitating a solution of the drug with a quantity of the IER until equilibrium complexation is achieved.

Generally, the batch method is preferred as it is simple and straightforward. A predetermined amount of drug is loaded onto the IER, the quantity added mainly influenced by the cation exchange capacity (which is a measure of an IER’s ability to hold exchangeable cations and therefore bind the API). The other factors that influence loading are the IER’s selectivity for the API, particle size, porosity and degree of crosslinks.

To start, it is important to identify the most ideal IER for the API. If not sure, consult your supplier for guidance. However, a simple screening process can be done that involves preparation of 1% w/v API solution to which the IER is added in different ratios, e.g 1:1, 1:2, 1:3, etc. The blends are stirred for up to 20 hours and sample solutions taken at regular interval in order to assay for free, uncomplexed drug. The most suitable IER is then one with the lowest amount of free drug (concentration remaining in solution).

The process is illustrated below:

Once the equilibration is completed, the IER-API complex can be washed, and used as is in syrups and suspensions or dried and blended with other excipients and compressed into tablets of choice or filled into capsules.

 

Usability Rating

References

Martel, J. J et al., 1981. Acid type ion Exchange resins and their use as medicines and compositions containing them. Patent EP27768.

Felton, L. A., 2018. Use of polymers for taste-masking pediatric drug products. Drug Devt Ind. Pharm 44, 1049 – 1055.

 

The Future of Science Events Post-COVID?

What’s the Future of Science Events Post-COVID?

May 25, 2021

It’s a cliché, I know, but COVID-19 has had an impact like nothing before on the events industry, and scientific conferences have not been spared. The arrival of the pandemic put brakes on all substantive meetings and conferences, and save for a few hybrid events here and there, it has not been the same since March 2021. Fifteen months on we are still some way before some semblance of normalcy returns when venues and public gatherings will be allowed to operate at full capacity.

Why Events Still Matter

A major activity in the life of a scientist, regardless of the role or sector, is the professional event, such as conference or meeting. Events provide an important space for practitioners to present their work, gain new skills, and acquire fresh ideas that can help further their research/careers.

Events are also important for brainstorming, networking and making vital connections with other scientists and suppliers and can lead to new initiatives, papers and funding. This is why scientific events matter.

From an economic viewpoint, events are a global force, contributing $1.2 trillion to the global economy through direct spend by delegates, attendees and organisers, as well as the millions of jobs supported, directly and indirectly.

The most popular scientific events, ranked by aggregated attendance, are seminars and corporate events, conferences and exhibitions, trade shows and fairs, and product launches. Interphex (mainly US-based), CPhI (Europe, US and Asia) and AAPS (US-based) represent the most prominent events and meetings annually on the pharmaceutical events calendar.

A Change to the Hybrid Model

With the pandemic raging, travel halted, budgets tightened and venues ordered to close, the events sector was forced to rethink and remodel their operations. Smart event organizers saw virtual events as an alternative, opening up opportunities that had never existed in the events industry before. Organisers had a lot of trial and testing to do in order to transition online. And people were excited by the idea of attending virtually as the “new normal”.

Virtual events offered a much needed break for organisers and permitted meetings to continue. As the situation improved, some organisers moved to hybrid events, which allowed some delegates to meet in person whilst also communicating with others virtually.

The hybrid innovation has allowed companies to continue to offer and run events much more frequently, and so far, this does not look like a temporary shift.

And although the number of physical attendees is restricted, hybridization allows extension of the event’s reach geographically, making it more cost effective and a more inclusive experience for both planners and attendees, a real positive. Moreover, as the content can be recorded it can be reused over and over again, increasing its life span.

Hybridisation represents a fundamental change in how events will work in the future, and hopefully, now means even greater engagement by companies and attendees.

The only problem, though, is that virtual events are cutting out most of the supply chain. Suddenly, venues are no longer in as high a demand as was before. Neither are caterers, furniture rentals, sound and lighting engineers, cleaners, and exhibition stand builders. All of these roles are being scaled back with the increasing resort to virtual events.

What Returns and What Changes?

There is no doubt that physical events will bounce back. Science is after all a social endeavour, and as scientists we thrive through physical interaction with other scientists and other humans. Getting back to normal, however, will take a while, and during this time, scientific meetings and events will more likely look very different. Expect more sophisticated virtual participation options, smaller satellite events complementing larger gatherings, and targeted events as people carefully weigh benefits and risks of attending events.

This year, and probably most of 2022, travel will likely remain complicated. But as more positive shoots of economic recovery emerge and bloom, the sector will bounce back strongly. Below is how events professionals predict the industry developing:

Annual general meetings and conferences

The annual general meeting and conference has been and will still remain the main platform for meeting, networking and exchange. Pre-pandemic, the annual meeting and conference typically attracted 500+ attendees, convening centrally, and interacting closely. But in the age of Covid-19, conferences do not sit well with social distancing requirements. This has made them nearly impossible to hold – both logistically, due to travel restrictions, and as a matter of public health.

When they return, the annual conference and meeting will likely look very different. You can expect shorter, more sophisticated events, with more virtual participation options, greater use of event technology, mobile apps and social media. We will likely see event split between the main event (50 to 100 attendees) and many more break-out, intimate sessions of anywhere between 10 – 15 attendees.

Satellite Events

With mass meetings being one of the proven vehicles of spreading COVID-19, it is understandable why people will be sceptical about attending live conferences soon. Therefore, smaller events with a manageable audience are the immediate future of the industry. You can expect to see smaller satellite events aimed at complementing larger gatherings. So if the main event is in London, you might have smaller hubs in Frankfurt, and Madrid.

Targeted Events

For a long time now, many organisations have been questioning the ROI on tradeshows and conferences. So while interest in targeted events, such as roadshows, trunk shows and townhall meetings, had been growing, we will see interest in these grow. The advantages of roadshows is that they can either be stand-alone events or a series of identical meetings taking place sequentially in multiple locations and allow companies to take their message out and meet targeted audiences face to face. Think of it as the event going to where the audience is rather than the audience coming to the event.

Event Technologies

Event technology is a term used to describe all of the digital tools, apps and software used in the events industry. Everything from check in & registration, to diagramming, to social media tools, and more can be considered event technology.

Acceptance of event technologies has been increasing over time and we now should expect event organisers and planners to increasingly leverage technology not only to manage COVID-19 risks but also to improve attendee experiences.

Takeaways

The pandemic has forced the event industry to adapt to various challenges at an unprecedented speed. This has even pushed event planners to innovate, as exemplified by increasing adoption of hybrid and virtual eventing.

Although virtual events bring the benefits of removing time and space constraints and increase participation, the need for social interaction cannot be dismissed.

Going forward, we can be sure to see changes in the way scientific events are delivered, including greater use of technologies, shorter, more intimate physical events and many other as yet to be implemented innovations.

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