1. Introduction
One of the most common applications of pH-responsive polymers, is in the formation of protective coatings of pharmaceutical formulations for oral delivery. It is desirable for pharmaceutical formulations to be delivered through oral administration via the stomach or intestines, and therefore, formulations are often designed to be highly soluble once the target environment is reached [
1]. For example, if the active drug is acid labile and loses functionality when exposed to the low-pH gastric environment (pH 1.5–3.5) a pH-responsive coating can be used to prevent the release of the formulation until the higher pH of the intestines (pH 5–6) is reached [
2]. These types of intestine-targeting polymer coatings are termed ‘enteric’ and commonly incorporate polyvinyl acetate and methacrylic acid-ethyl acrylate copolymers [
1,
2,
3]. In contrast, when drug dissolution within the stomach is desired, ‘reverse-enteric’ coatings are employed. Reverse-enteric coatings prevent dissolution within the higher pH oral environment (pH 5–7), but dissolve rapidly once the low-pH gastric environment is reached [
1]. Generally, reverse-enteric coatings are used for taste-masking to avoid patient non-compliance due to an unpalatable pharmaceutical formulation [
2], and employ tertiary amine-based acrylate copolymers. These polymers are commonly synthesised via conventional free-radical polymerisation (CFRP) [
4].
Prominent examples of commercially available polymers used for reverse enteric coatings include the Eudragit
® family (Eudragit
® E 100, E12.5, and E PO). Reviewed elsewhere [
5], these polymers are commonly used for immediate-release formulations that require taste-masking. Available in a range of forms, including granules (E 100), organic solutions (E 12.5), and powders (E PO), these Eudragit
® polymers are soluble in the gastric environment (and at pH values < 5) and insoluble at elevated pH (pH values > 5) [
5]. Reverse enteric Eudragit polymers have been used in the production of a range of taste masked dosage forms, such as microparticles [
6], beads [
7], capsules [
8], and 3D printed [
9] or pan coated [
10] tablets. However, the complete containment, and effective taste-masking of bitter-tasting active pharmaceutical ingredients (APIs) within the oral cavity remains challenging to mediate. Unique challenges are posed by the properties of reverse enteric copolymers (e.g., the swelling and permeability characteristics of Eudragit
® copolymers), and the required dosage form.
For dosage forms that do not prevent contact between the bitter API and the oral cavity (pH 6.8–7.4) [
11], such as microbeads (or microparticles) composed of a spherical matrix containing a mixture of the reverse enteric polymer and API, the encapsulated API is often prematurely released within the oral cavity [
12]. As a result, the bitter taste of the API is only suppressed when relatively large amounts of the constitutive reverse enteric polymer are used, which limits the capacity for drug loading. For example, microbeads containing propranolol hydrochloride were prepared with Eudragit
® E PO via prilling, to produce a taste-masked paediatric formulation for oral administration [
7]. The greatest taste-masking was achieved with microbeads exhibiting a 1:25 ratio of propranolol:matrix (equivalent to ~96%
w/
w matrix). While the formulation limited the release of propranolol to 3.3% following 2.5 min at pH 6.8, this could only be achieved at a low drug loading of ~38 mg·g
−1 (mg of propranolol per g of microbead, equivalent to ~3.8%
w/
w propranolol) [
7]. Low drug loadings may be problematic for APIs that require high doses or dosage forms with size considerations, and the use of large amounts of reverse enteric polymer may raise concerns for patient safety [
6].
Dosage forms that provide a barrier between the bitter API and the oral cavity, such as microcapsules (also called micropellets) bearing reverse enteric film coatings, can exhibit more efficient taste-masking properties. For example, microcapsules containing the antiprotozoal drug ornidazole were film coated via fluidised-bed spray coating, with the reverse enteric polymer Kollicoat
® Smartseal 30D, at a 40%
w/
w mass gain [
13]. The microcapsules limited release of ornidazole to ≤5% following 5 min at pH 6.8, and only reached <15% after 120 min. Comparatively, similar performance to the Eudragit
® E PO microbeads was achieved with significantly less of the Kollicoat
® material. Further, when a similarly high ratio of Kollicoat
® to drug was used (80%
w/
w, cf., 96%
w/
w), superior taste-masking performance was achieved, as no ornidazole was released in 120 min. Whilst microcapsules are advantageous for improved taste-masking performance, microbeads can exhibit more rapid drug release within the gastric environment. In the previous examples, the Eudragit
® microbeads achieved 100% drug release within 5 min (pH 1.2) [
7], whereas the Kollicoat
® microcapsules achieved ~90% release within 45 min (pH 1.0) [
13]. In many cases, the selection of a commercially available reverse enteric polymer and the dosage form it is incorporated into, requires a trade-off between taste-masking performance, and rapid release within the gastric environment.
The limited drug loading and release of APIs under simulated oral cavity conditions for certain formulations highlights the need for reverse enteric coatings that effectively contain bitter APIs and mediate rapid release within the gastric environment. However, in the development of new reverse enteric coatings, their intended application method is an important consideration. Film coating via spray atomisation is one of the most common and facile methods for coating pharmaceutical formulations [
14]. This process involves dissolving the polymer in a solvent (organic or aqueous) before atomising the solution using compressed air. The droplets formed during atomisation deposit and spread across the substrate, and as the solvent evaporates a film is formed. Although various types of equipment can be used, processing utilising a fluidised-bed is favourable as it affords high drying efficiency and is compatible with coating formulations dispersed or solubilised in either aqueous or organic solvents [
1,
15]. Furthermore, the diminutive size of ‘benchtop’ fluidised-bed instruments makes them highly suited to laboratory-scale prototyping, as small batches (~500 g) can be readily produced [
16].
In the current work, we report the synthesis and characterisation of a series of novel pH-responsive copolymers and evaluate their application as reverse-enteric coatings via fluidised-bed spray coating. 2-Vinylpyridine (VP) was selected as the pH-responsive moiety through which to develop an appropriately pH-responsive polymer. Given the reported
pKa value of poly(2-vinylpyridine) (PVP) homopolymers (~4.5 [
17]), it was hypothesised that via addition polymerisation with a methacrylate monomer(s), a pH-responsive copolymer with suitable pH-responsiveness and compatibility with fluidised-bed spray coating, could be synthesised. Due to the differences in
Tg values exhibited by homopolymers of VP compared to butyl methacrylate (BMA) (PVP
Tg = 104 °C [
18], PBMA
Tg = 20–55 °C [
18]), incorporation of different ratios of VP and BMA in a random copolymer, may enable tuning of the
Tg values of resultant copolymers to an appropriate processing temperature, whilst maintaining pH-responsivity. For example, when fluidised-bed spray coating an aqueous dispersion, the minimum film-formation temperature (MFF) is impacted by the
Tg value of the constitutive pH-responsive copolymer [
19]. An appropriate
Tg value is required to ensure the MFF temperature is below the spray coating temperature, to facilitate coalescence of the polymer particles and cohesive film formation. Two additional, high-
Tg (cf., BMA) monomers—methyl methacrylate (MMA) and isobornyl methacrylate (IBMA)—were selected as additional target monomers to make a range of
Tg values accessible, as homopolymers of MMA or IBMA generally exhibit higher
Tg values than homopolymers of BMA or VP (i.e., PMMA
Tg = 38–150 °C [
18] and PIBMA
Tg = 170–206 °C [
20]). Further, the mol% fraction of VP in the copolymer structure, and incorporation of comparatively hydrophobic monomers, would also alter the hydrophilicity of the resultant copolymer and enable the tuning of water absorption and solubility of a coating as a result.
To that end, a library of pH-responsive copolymers was synthesised with varying ratios of VP and BMA, and MMA or IBMA. The physicochemical properties of these copolymers were investigated, to determine which copolymers exhibited favourable solubility (insoluble at pH 7.4, soluble at pH < 2), low water absorption, and a suitable glass transition temperature (Tg) to enable spray coating. These properties were considered necessary to afford a uniform and cohesive coating following spray coating. The physicochemical properties of the synthesised copolymers were investigated through solubility, water absorption, and thermal analysis experiments. Selected copolymers were evaluated for their compatibility with fluidised-bed spray coating and potential effectiveness as reverse enteric coatings for taste-masking.
2. Materials and Methods
2.1. Materials
All reagents were used as received unless otherwise specified. 2-Vinylpyridine (VP, 97%), butyl methacrylate (BMA, 99%), methyl methacrylate (MMA, 99%), and isobornyl methacrylate (IBMA, 92.5%) were purchased from Sigma-Aldrich (St. Louis, MO, USA). Inhibitors were removed from vinyl and methacrylate monomers via basic aluminium oxide before use. Azobisisobutyronitrile (AIBN, 12% w/w in acetone), poly(ethylene glycol) (number average molecular weight (Mn) = 10 kDa, PEG 10k), rhodamine b (RhB, ≥95%), basic aluminium oxide, lithium chloride (LiCl, technical grade) and deuterated chloroform (CDCl3), were purchased from Sigma-Aldrich (St. Louis, MO, USA). Analytical grade 1,4-dioxane, ethanol (EtOH, 100% undenatured), potassium chloride (KCl), hydrochloric acid (HCl, 36.5–38.0%), sodium acetate (NaOAc), and HPLC grade tetrahydrofuran (THF) and dimethylformamide (DMF) were purchased from ChemSupply (Gillman, Australia). Poly(methyl methacrylate) (PMMA) standards for gel permeation chromatography (GPC) were purchased from Polymer Standards Service GmbH (Mainz, Germany). Phosphate buffered saline (PBS) tablets were purchased from Sigma-Aldrich (St. Louis, MO, USA). Solutions for PBS were prepared per the manufacturer’s guidelines. An Arium Pro Ultrapure Water System (Sartorius, Goettingen, Germany) was used to produce high-purity water (≥18.2 MΩ·cm). pH 1.5 solutions were prepared from KCl (0.2 M) and HCl (0.2 M). Nitrogen and argon (Ar) (ultra-high purity, ≥99.999%) gases were purchased from BOC Ltd. (North Ryde, Australia). Suglets® sugar spheres (12/14 mesh, 1.4–1.7 mm diameter) were provided by Colorcon® (Scoresby, Victoria, Australia).
2.2. Instrumentation
Gas chromatography (GC) was performed on a Shimadzu GC-2010 gas chromatograph (Kyoto, Japan). Proton nuclear magnetic resonance spectroscopy (1H NMR) was conducted on a Bruker Avance III HD 600 MHz spectrometer (Billerica, MA, USA). GPC was performed using a Shimadzu Prominence liquid chromatography (LC) system (Kyoto, Japan), fitted with a differential refractive index detector (Shimadzu, RID-20A) and two Shimadzu columns in series (GPC-80MD and GPC-804D). Modulated differential scanning calorimetry (MDSC) and thermogravimetric analysis (TGA) were conducted using TA Instruments (New Castle, WY, USA) DSC 250 and TGA5500, respectively. Ultraviolet-visible (UV-vis) spectrophotometry was performed on an Evolution 260 Bio spectrophotometer, and temperature-controlled using a single-cell Peltier system (Thermo Scientific, Waltham, MA, USA). Fluidised-bed spray coating was conducted using a benchtop Mini Coater/Drier 2 (Caleva Process Solutions Ltd., Dorset, UK).
2.3. Procedures
2.3.1. Synthesis of Poly[(2-vinylpyridine)x-co-(butyl methacrylate)y]
The copolymers of poly[(2-vinylpyridine)x-co-(butyl methacrylate)y] (PVB x/y) were synthesised with x:y ratios of 40:60, 50:50, and 60:40 mol% (VP:BMA). A representative description of the synthesis of PVB 50/50 is provided.
Inhibitor-free VP (25.6 mL, 238 mmol) and BMA (37.8 mL, 238 mmol) (mol% VP:BMA 50:50), and AIBN solution (6.51 mL, 4.8 mmol)) were combined ([total monomer]:[initiator] 100:1 mole ratio) in 1,4-dioxane (50%
v/
v) under an inert atmosphere (Ar) and heated at reflux with stirring. Additional AIBN solution (6.51 mL, 4.8 mmol) was added after 1 and 2 h to maximise monomer conversion. After 3 h, the reaction was cooled (~25 °C), the crude reaction mixture (CRM) was diluted with THF (~20%
v/
v), and the copolymer product precipitated from hexanes (1:10
v/
v CRM:hexanes) in a conical flask. The supernatant was decanted, and the precipitate was redissolved in THF (~75 mL), transferred to a round-bottomed flask, concentrated in vacuo (40 °C, 10 mbar), and then dried in vacuo (23 °C, 0.02 mbar) to afford the polymer as a pale-yellow solid. The percentage of monomer conversion (determined by GC) was 95% and the isolated yield was >99%. GPC
Mn = 16.2 kDa,
Mw = 31.9 kDa,
Ð = 1.97.
1H NMR (600 MHz, 25 °C, CDCl
3) δ
H 8.45 (br s, CH, VP repeat unit (RU)), 7.44 (br s, CH, VP RU), 6.99–6.50 (m, CH, VP RU), 3.87 (br s, OCH
2, BMA RU), 3.53–2.32 (m, CH, VP RU), 2.32–1.02 (m, CH
2, BMA and VP RUs), 1.02–0.16 (m, CH
3, BMA RU) ppm. GPC chromatograms and
1H NMR spectra of the PVB copolymers are provided in the
Supplementary Materials,
Figures S1 and S2, respectively.
2.3.2. Synthesis of Poly[(2-vinylpyridine)x-co-(butyl methacrylate)y-co-(methyl methacrylate)z]
The copolymers of poly[(2-vinylpyridine)x-co-(butyl methacrylate)y-co-(methyl methacrylate)z] (PVBM x/y/z) were synthesised with x:y:z ratios of 40:50:10, 30:50:20, 30:40:30, and 40:40:20 mol% VP:BMA:MMA. A representative description of the synthesis of PVBM 40:50:10 is provided.
Inhibitor-free VP (20.5 mL, 190 mmol), BMA (37.8 mL, 238 mmol) and MMA (5.07 mL, 47 mmol) (mol% VP:BMA:MMA 40:50:10), and AIBN solution (6.51 mL, 4.8 mmol)) were combined ([total monomer]:[initiator] 100:1 mole ratio) in 1,4-dioxane (50%
v/
v) under an inert atmosphere (Ar) and heated at reflux with stirring. Additional AIBN solution (6.51 mL, 4.8 mmol) was added after 1 and 2 h to maximise monomer conversion. After 3 h, the reaction was cooled (~25 °C), the CRM was diluted with THF (~20%
v/
v), transferred to a round-bottomed flask, and the copolymer product was obtained by drying the CRM in vacuo (10 mbar, 80 °C). The copolymer product was obtained as a pale-yellow solid. The percentage monomer conversion (determined by GC) was 99% and the isolated yield was >98%. GPC
Mn = 14.8 kDa,
Mw = 32.4 kDa,
Ð = 2.19.
1H NMR (600 MHz, 25 °C, CDCl
3) δ
H 8.45 (br s, CH, VP repeat unit (RU)), 7.41 (br s, CH, VP RU), 6.97–6.50 (m, CH, VP RU), 3.90 (br s, OCH
2, BMA RU), 3.54 (br s, OCH
3, MMA RU), 3.25–2.07 (m, CH, VP RU), 2.07–1.01 (m, CH
2, VP, BMA and MMA RU), 1.01–0.13 (m, CH
3, BMA RU) ppm. GPC chromatograms and
1H NMR spectra of the PVBM copolymers are provided in the
Supplementary Materials,
Figures S1 and S3, respectively.
2.3.3. Synthesis of Poly[(2-vinyl pyridine)x-co-(butyl methacrylate)y-co-(isobornyl methacrylate)z]
The copolymers of poly[(2-vinylpyridine)x-co-(butyl methacrylate)y-co-(isobornyl methacrylate)z] (PVBI x/y/z) were synthesised with x:y:z ratios of 50:45:5, 50:40:10, 50:35:15, 50:30:20, and 40:40:20 mol% VP:BMA:IBMA. A representative synthesis of the PVBI 50:30:20 copolymer is given below.
Inhibitor free VP (20.50 mL, 190 mmol), BMA (18.00 mL, 113 mmol), and IBMA (17.25 mL, 76. mmol), and AIBN solution (5.25 mL, 3.1 mmol) were combined ([total monomer]:[initiator] 122:1 mole ratio) in 1,4-dioxane (50%
v/
v) under an inert atmosphere (Ar) and heated at reflux with stirring. AIBN (5.25 mL, 3.1 mmol) was added again after 1 and 2 h to maximize monomer conversion. After 3 h, the reaction was cooled (~25 °C), and the solvent was removed in vacuo. Further drying was conducted at 80 °C in vacuo (0.01 mbar) to afford the polymer as a pale-yellow solid. The percentage conversion (determined by GC) was >99%, and the isolated yield was >98%. GPC
Mn = 17.7 kDa,
Mw = 34.0 kDa,
Đ = 1.92.
1H NMR (600 MHz, 25 °C, CDCl
3):
δH 8.40 (br s, CH, VP repeat unit (RU)), 7.39 (br s, CH, VP RU), 7.10–6.20 (m, CH, VP RU), 4.45−3.05 (m, OCH
2, BMA RU; OCH, IBMA RU), 3.00–2.05 (m, CH, VP RU), 1.97−1.0 (m, CH
2, VP, BMA and IBMA RU; CH, IBMA RU), 0.97–0.45 (m, CH
3, BMA and IBMA RU) ppm. GPC chromatograms and
1H NMR spectra of the PVBI copolymers are provided in the
Supplementary Materials,
Figures S1 and S4, respectively.
2.3.4. Gas Chromatography
Syntheses were monitored by analysing 50 µL aliquots of the CRM diluted in DCM (1.5 mL) at predetermined time points. Monomer consumption was determined from the relative decrease in peak area compared to their pre-polymerisation (t0) concentrations, using 1,4-dioxane as an internal reference. Fitted with a flame ionisation detector (FID) and a Supelco SPB-35 column (30.0 m × 0.25 mm, 0.25 µm) (Bellefonte, PA, USA) and using nitrogen carrier gas, the GC was operated in linear velocity mode. A linear velocity of 56.5 cm·s−1 was used, with the sample injection port and FID temperature both at 250 °C. For all samples, a split injection (split ratio 50:1) and injection volume of 1.0 µL were used, using a temperature program consisting of 40 °C (1 min hold) to 180 °C (2 min hold) at 22.50 °C·min−1.
2.3.5. Gel Permeation Chromatography
Synthesised copolymers were analysed for their molecular weight characteristics via GPC. The Shimadzu LC system was operated at a column oven temperature of 40 °C, and a flow rate of 1 mL·min−1, using THF as the eluent. Prior to injection at an injection volume of 50 µL, copolymer samples (5 mg·mL−1) were filtered using 0.45 µm nylon syringe filters. A conventional column calibration of narrow molecular weight PMMA standards was used to determine the molecular weight characteristics of the copolymers, via the Shimadzu LabSolutions software (v5.93). The above parameters were used to determine the solubilities of the synthesised copolymers, except with a column oven temperature of 70 °C and an eluent consisting of 0.1 M LiCl in DMF.
2.3.6. Modulated Differential Scanning Calorimetry
MDSC analyses were conducted on powdered copolymer samples (~5–10 mg) in standard aluminium pans, under nitrogen flow (cell purge flow rate, 50 mL·min−1). Samples were heated from −80 to 250 °C at a ramp rate of 3 °C·min−1, using a modulation period of 40 s, and a modulation temperature amplitude of ±64 °C. The Universal Analysis software (v4.5A) (TA Instruments, New Castle, WY, USA) was used to determine the Tg values of each copolymer, from the point of inflection between the onset and end temperatures of the transition, in the reversing heat flow (W·g−1) curves.
2.3.7. Thermogravimetric Analysis
TGA analyses were conducted on powdered copolymer samples (~10 mg) in platinum pans, under nitrogen flow (sample purge flow rate, 25 mL·min−1). Samples were heated from 30 to 600 °C, at a ramp rate of 20 °C·min−1. The onset values for the thermal degradation of each copolymer were determined from the derivative weight (%·°C−1) curves. Weight loss values were determined from the step change of the major degradation event observed in the weight (%) curves. Both the onset and weight loss values were determined using TA Instruments Universal Analysis software (v4.5A).
2.3.8. Copolymer Water Absorption
A 15-ton hydraulic press was used to prepare powdered copolymer samples (~150 mg) as discs (13 mm diameter × 1.2 mm height). The copolymer discs were dried for 72 h in vacuo (0.01 mbar, 23 °C), then weighed and submerged in PBS (20 mL, pH 7.4) in sealed vials and stored at 37 °C. The copolymer discs were removed periodically from the solution and any solution present on the disc surface was removed using lint-free tissue paper (Kimwipes™) prior to weighing. The mass of the absorbed PBS solution was then calculated from the increase in disc mass. The copolymer discs were monitored for 40–60 d. All copolymers were analysed in triplicate, and water absorption values were reported as the mean ± std. dev.
2.3.9. Copolymer Solubility
Powdered copolymer samples (~10 mg) were combined with 1 mL of a pH 1.0, 1.5, or 2.0 solution, in microcentrifuge tubes. The tubes were rotary mixed for 48 h at 37 °C, then centrifuged (15 krpm, 3 min), to separate the solubilised copolymer in the supernatant solution, and the insoluble copolymer solid. A 50 μL aliquot of the supernatant was removed, diluted (1:10) in GPC mobile phase (0.1 M LiCl in DMF) and analysed via GPC. The peak area of the copolymer was correlated to a calibration curve (vide infra), to determine the concentration of the copolymer in the sample, and therefore, its solubility.
Seven-point calibration curves were prepared for each copolymer by correlating the known mass of a copolymer standard to its peak area value obtained via GPC analysis (
Supplementary Materials,
Figure S5). Copolymer standards were prepared by vortex mixing (2 krpm) a 10 mg sample in a pH 1.0 solution (1 mL, 10 mg·mL
−1) until homogeneity, and conducting a 1:10 dilution in the mobile phase. Each copolymer standard was analysed via GPC at injection volumes from 10–100 µL, to afford a seven-point calibration curve.
2.3.10. Ultraviolet-Visible Spectrophotometry
UV-vis spectrophotometry was conducted at 37 °C using a quartz cuvette (l = 10 mm) and stirred at the maximum stirring rate during analysis.
2.3.11. Fluidised-Bed Spray Coating
A model drug formulation was prepared by solubilising PEG 10 kDa (7.5 g) and RhB (1.3 g) in 70:30% v/v EtOH:water (170 mL). The model drug formulation was introduced to the spray coater via a syringe pump operating at a flow rate of 15.2 mL·h−1 and atomised using an atomising air pressure of 5 PSI. Suglets® (n = 1800) were fluidised with a fan speed of 90% and fluidisation air temperature of 40 °C, throughout the coating. The formulation was applied in a single coating cycle (45 min), after which the coated Suglets® were dried in vacuo (0.02 mbar, 23 °C, 16 h), and stored in a desiccator prior to use.
Reverse enteric copolymer coating formulations were prepared by solubilising PVB 40/60, PVB 60/40, PVBM 40/50/10, or PVBM 30/50/20 in EtOH (50 mL). Reverse enteric copolymer coatings were applied using the same parameters as the model drug formulation, except the fluidisation air temperature was set to ambient temperature (23 °C). Suglets® (n = 340) were coated in two cycles (45 min each, 90 min total) for each copolymer, to afford weight gains of 4.9–6.5% w/w. The coated Suglets® were dried in vacuo after the first cycle (0.02 mbar, 23 °C, 20 min), and again after the second (16 h), then stored in a desiccator prior to use.
2.3.12. Taste-Masked Formulation Stability
A simulated salivary fluid (phosphate-buffered, pH 6.8 solution) was prepared from a pH 7.4 PBS solution, via the addition of 0.1 M HCl. Suglets® coated with both the model drug formulation and a reverse enteric copolymer coating were submerged in a pH 6.8 solution (3.0 mL) and stored at 37 °C, to mimic human salivary conditions. Samples were monitored periodically, and taste-masking failure was determined qualitatively, by the presence of RhB in the receiving solution.
2.3.13. Taste-Masked Formulation Release
Suglets® coated with both the model drug formulation and a reverse enteric copolymer coating were suspended in a pH 1.5 solution (3.5 mL) at 37 °C, under stirring, to mimic the human gastric environment. The presence of RhB in the receiving solution was monitored inline by UV-vis spectrophotometry (λmax = 556 nm), to determine the initial and complete release times of RhB.
4. Conclusions
A series of pH-responsive copolymers were synthesised via conventional free radical polymerisation, to produce copolymers suitable for taste-masking. VP constituted the pH-responsive moiety, and was copolymerised with BMA, BMA and MMA, or BMA and IBMA, in varying mol% fractions, to investigate the effects on key physicochemical properties (Tg value, solubility, and water absorption) that affect the taste-masking properties of the resultant copolymers. For the PVB series, the Tg values, solubility and water absorption were all found to be positively correlated with the mol% fraction of VP. In contrast, in the PVBM series, the Tg values were positively correlated with the mol% fraction of MMA, whereas the solubility and water absorption properties were dependent on the mol% fraction of VP. In contrast to the PVB and PVBM series, the solubility, water absorption and Tg values of the PVBI copolymers were all found to be dependent on the mol% fraction of IBMA. Therefore, these properties could be tuned by fixing the mol% fraction of VP and altering the mol% fraction IBMA. Copolymers from the PVB and PVBM series were evaluated preliminarily for their taste-masking effectiveness, via fluidised-bed spray coating. Select copolymers were spray coated onto Suglets® bearing a model drug formulation containing RhB. PVB 40/60 and PVBM 40/50/10 copolymers exhibited excellent taste-masking properties, as they effectively contained RhB for up to 72 h in a simulated salivary environment (pH 6.8). In addition, Suglets® bearing either coating were found to rapidly release their RhB payload within 10 min in a simulated gastric environment (pH 1.5). In both cases, the favourable taste-masking properties were achieved with low mass gain (5.2–6.5% w/w). Whilst these results are preliminary—given the small batch sizes employed—with further evaluation the reported copolymers may enable the preparation of pharmaceutical formulations with improved taste-masking properties, using relatively low proportions of the copolymers in the resultant dosage form.