Evaluation of Polymer Mucoadhesiveness by the Use of Acoustic Spectroscopy

An innovative and simple methodology has been developed and used for the evaluation of mucoadhesive properties of several polymers by means of sound speed measurements using high-resolution acoustic spectroscopy. In systems made of polymers in water, variations in hydration shell of polymeric chains determine changes of dispersions compressibility, and this phenomenon can be monitored by sound speed measurements. Four different polymers have been selected, namely PEG 6000, Carbopol 974, HPMC K4M, and Pectin 200/USP, all characterised by very different mucoadhesive properties. Samples made of each polymer alone (0.3–1.0% w/w) or in mixture with mucin (mucin fixed at 1.0% w/w) in water were investigated while using high-resolution ultrasonic spectrometer at two different frequencies (5.2 and 8.2 MHz). Polymer–mucin interaction was evaluated comparing experimental sound speed values of polymer–mucin samples with their theoretical values derived from the addition of sound speeds obtained while analysing each component alone. Results demonstrated the ability of the acoustic method to discriminate between mucoadhesive and no mucoadhesive polymer–mucin dispersions and allowed also the comparison between their mucoadhesive strengths. The study has therefore demonstrated the potential of using high-resolution ultrasonic spectroscopy to evaluate the polymers’ mucoadhesiveness, with the great advantage of testing small amount of samples even if opaque.     

Heat-Induced Whey Protein Gels: Effects of pH and the Addition of Sodium Caseinate

The effects of pH (6.7 or 5.8), protein concentration and the heat treatment conditions (70 or 90 °C) on the physical properties of heat-induced milk protein gels were studied using uniaxial compression, scanning electron microscopy, differential scanning calorimetry, and water-holding capacity measurements. The systems were formed from whey protein isolate (10–15% w/v) with (5% w/v) or without the addition of caseinate. The reduction in pH from 6.7 to 5.8 increased the denaturation temperature of the whey proteins, which directly affected the gel structure and mechanical properties. Due to this increase in the denaturation temperature of the β-lactoglobulin and α-lactalbumin, a heat treatment of 70 °C/30 min did not provide sufficient protein unfolding to form self-supporting gels. However, the presence of 5% (w/v) sodium caseinate decreased the whey protein thermo stability and was essential for the formation of self-supporting gels at pH 6.7 with heat treatment at 70 °C/30 min. The gels formed at pH 6.7 showed a fine-stranded structure, with great rigidity and deformability as compared to those formed at pH 5.8. The latter had a particulate structure and exuded water, which did not occur with the gels formed at pH 6.7. The addition of sodium caseinate led to less porous networks with increased gel deformability and strength but decreased water exudation. The same tendencies were observed with increasing whey protein concentration.     

Whey Protein/Arabic Gum Gels Formed by Chemical or Physical Gelation Process

Whey proteins (WP) gelation process with addition of Arabic gum (AG) was studied. Two different driving processes were employed to induce gelation: (1) heating of 12% whey protein isolate (WPI) solutions (w/w) or (2) acidification of previous thermal denatured WPI solutions (5% w/w) with glucono-δ-lactone (GDL). Protein concentrations were different because they were minimal to form gel in these two processes, but denaturation conditions were the same (90 °C/30 min). Water-holding capacity and mechanical properties of the gels were evaluated. The BST equation was used to evaluate the nonlinear part of the stress–strain data. Cold-set gels were weaker than heat-set gels at the pH range near the isoelectric point (pI) of the main whey proteins, but heated gels were more deformable (did not exhibit rupture point) and showed greater elasticity modulus. However, gels formed by heating far from the pI (pH 6.7 or 3.5) showed more fragile structure, indicating that, in these mixed gels, there are prevailing biopolymers interactions. Cold-set and heat-set gels at pH near or below the WP pI showed strain-weakening behavior, but heated gels at neutral pH showed strong strain-hardening behavior. Such results suggest that differences in stress–strain curve at the nonlinear part of the data could be correlated to structure particularities obtained from different gelation processes.     

Nanocarrier for the Transdermal Delivery of an Antiparkinsonian Drug

The purpose of the present study was to investigate the potential of nanoemulsions as nanodrug carrier systems for the percutaneous delivery of ropinirole. Nanoemulsions comprised Capryol 90 as the oil phase, Tween 20 as the surfactant, Carbitol as the cosurfactant, and water as an external phase. The effects of composition of nanoemulsion, including the ratio of surfactant and cosurfactant (S _mix) and their concentration on skin permeation, were evaluated. All the prepared nanoemulsions showed a significant increase in permeation parameters such as steady state flux (J _ss) and permeability coefficient (K _p) when compared to the control (p < 0.01). Nanoemulsion composition (NEL3) comprising ropinirole (0.5% w/w), Capryol 90 (5% w/w), S _mix 2:1 (35% w/w), and water (59.5% w/w) showed the highest flux (51.81 ± 5.03 μg/cm²/h) and was selected for formulation into nanoemulsion gel. The gel was further optimized with respect to oil concentration (Capryol 90), polymer concentration (Carbopol), and drug content by employing the Box–Behnken design, which statistically evaluated the effects of these components on ropinirole permeation. Oil and polymer concentrations were found to have a negative influence on permeation, while the drug content had a positive effect. Nanoemulsion gel showed a 7.5-fold increase in skin permeation rate when compared to the conventional hydrogel. In conclusion, the results of the present investigation suggested a promising role of nanoemulsions in enhancing the transdermal permeation of ropinirole.     

Solid�CLiquid Transitions and Stability of HPKO-in-Water Systems Emulsified by Dairy Proteins

Stability of oil-in-water emulsions during freezing and thawing is regulated by the phase transitions occurring in the continuous and dispersed phases upon thermal treatments and by the composition of the interfacial membrane. In the present study, the impact of the water phase formulation (0–2.5–5–10–20–30–40% w/w sucrose), the interfacial composition [whey protein isolates (WPI) or sodium caseinate (NaCas) used at different concentrations], and the particle size on the stability of hydrogenated palm kernel oil (30% w/w)-in-water systems was investigated. Phase/state behaviour of the continuous and dispersed phases and emulsion destabilisation were studied by differential scanning calorimetry. System morphology was observed by particle size analysis and optical microscopy. The presence of sucrose in the aqueous phase and reduced particle size distribution significantly improved emulsion stability. WPI showed better stabilising properties than NaCas at lipid to protein ratios of 10:1, 7.5:1, 5:1 and 4:1. Increased WPI concentration significantly improved emulsion resistance to breakdown during freeze–thaw cycling. NaCas showed poor stabilising properties and was ineffective in reducing emulsion destabilisation at 0% sucrose at all the lipid to protein ratios.     

Polymerization of guaiacol by lignin-degrading manganese peroxidase from Bjerkandera adusta in aqueous organic solvents

 Lignin-degrading manganese (II) peroxidase (MnP) purified from the culture of a wood-rotting basidiomycete, Bjerkandera adusta, was used in the polymerization of guaiacol. MnP was found to catalyze polymerization of guaiacol in 50% aqueous acetone, dimethyl formamide, methanol, ethanol, dioxane, acetonitrile, ethylene glycol and methylcellosolve. Maximum yield of polyguaiacol was achieved in 50% aqueous acetone. The weight average molecular weight (M _w) of the polymer was estimated to be 30 300 by gel permeation chromatography. However, matrix-assisted laser desorption ionization time of flight mass spectroscopy (MALDI-TOF-MS) analysis gave a more reliable M _w of 1690. IR, ¹³C-NMR, MALDI-TOF-MS and pyrolysis GC-MS analyses showed the presence of C–C and C–O linkages and quinone structure in polyguaiacol. It was also indicated that polyguaiacol has a methoxy-phenyl group as the terminal moiety. This suggests that polyguaiacol is a branched polymer in which guaiacol units are cross-linked at the phenolic group. Thermal gravimetric and differential scanning calorimetric analyses were also carried out. MnP also catalyzed the polymerization of o-cresol, 2,6-dimethoxyphenol and other phenolic compounds and aromatic amines. M _w of these polymers ranged from around 1000 to 1500. Received: 2 August 1999 / Received revision: 10 December 1999 / Accepted: 4 January 2000     

Improved Albendazole Dissolution Rate in Pluronic 188 Solid Dispersions

Solids dispersions (SDs) have been proposed as an alternative to improve the dissolution rate of low solubility drugs. SDs containing albendazole (ABZ; 5, 10, 25, and 50% w/w) and Pluronic 188 (P 188) as hydrophilic carrier were formulated. The obtained SDs were assessed in comparison to physical mixtures (PMs). Drug–polymer interactions in solid state were investigated using Fourier-transform infrared spectroscopy, scanning electron microscopy, and X-ray diffraction analysis. No chemical interaction was found between ABZ and poloxamer. The dissolution profiles indicated that ABZ incorporated in SDs and PMs was rapidly released, reaching rapidly the steady state. Increased dissolution rates are usually observed at the highest polymer proportions. However, an opposite effect for SDs as well as for PMs was observed in the assays described here. The systems with the lowest P 188 percentages (SD4, SD3; PM4, PM3) tended to be more effective in increasing the ABZ dissolution rate. Such a result can be attributed to the fact that concentrated aqueous solutions of Poloxamer may form thermo-reversible gels. The physical–mechanical properties indicated that SDs possess improved flow and compacting properties compared to PMs. Thus, ABZ SDs would be more convenient for solid dosage form design and manufacture.     

Stability Assessment of Injectable Castor Oil-Based Nano-sized Emulsion Containing Cationic Droplets Stabilized by Poloxamer–Chitosan Emulsifier Films

The objectives of the present work were to prepare castor oil-based nano-sized emulsion containing cationic droplets stabilized by poloxamer–chitosan emulgator film and to assess the kinetic stability of the prepared cationic emulsion after subjecting it to thermal processing and freeze–thaw cycling. Presence of cryoprotectants (5%, w/w, sucrose +5%, w/w, sorbitol) improved the stability of emulsions to droplet aggregation during freeze–thaw cycling. After storing the emulsion at 4°C, 25°C, and 37°C over a period of up to 6 months, no significant change was noted in mean diameter of the dispersed oil droplets. However, the emulsion stored at the highest temperature did show a progressive decrease in the pH and zeta potential values, whereas the emulsion kept at the lowest temperatures did not. This indicates that at 37°C, free fatty acids were formed from the castor oil, and consequently, the liberated free fatty acids were responsible for the reduction in the emulsion pH and zeta potential values. Thus, the injectable castor oil-based nano-sized emulsion could be useful for incorporating various active pharmaceutical ingredients that are in size from small molecular drugs to large macromolecules such as oligonucleotides.     

Studies on the Effect of Water-Soluble Polymers on Drug–Cyclodextrin Complex Solubility

The effect of complexation of irbesartan (IRB), a practically water-insoluble drug, with cyclodextrins in presence of different concentrations of water-soluble polymers (PEG 4000 and PVP K-90) on the dissolution rate of the drug has been investigated. Phase solubility studies were carried out to evaluate the solubilizing power of βCD in association with water-soluble polymers towards IRB and to determine the apparent stability constant (K _S) of the complexes. Improvement in K _S value for ternary complexes (IRB–βCD–polymers) clearly proved the benefit on the addition of water-soluble polymer to increase complexation efficiency. The dissolution rate of the drug from ternary systems containing PEG 4000 and PVP K-90 was higher as compared to the binary system. An optimum increase in the dissolution rate of the drug was observed at a polymer concentration of 5% w/w for PVP K-90 and 10% w/w for PEG 4000. DSC, FTIR, SEM, and XRD studies were carried out to characterize the complexes.     

Effect of Soy Protein Subunit Composition on the Rheological Properties of Soymilk during Acidification

The effect of soy protein subunit composition on the acid-induced aggregation of soymilk was investigated by preparing soymilk from different soybean lines lacking specific glycinin and β-conglycinin subunits. Acid gelation was induced by glucono-δ-lactone (GDL) and analysis was done using diffusing wave spectroscopy and rheology. Aggregation occurred near pH 5.8 and the increase in radius corresponded to an increase in the elastic modulus measured by small deformation rheology. Diffusing wave spectroscopy was also employed to follow acid gelation, and data indicated that particle interactions start to occur at a higher pH than the pH of onset of gelation (corresponding to the start of the rapid increase in elastic modulus). The protein subunit composition significantly affected the development of structure during acidification. The onset of aggregation occurred at a higher pH for soymilk samples containing group IIb (the acidic subunit A₃) of glycinin, than for samples prepared from Harovinton (a commercial variety containing all subunits) or from genotypes null in glycinin. The gels made from lines containing group I (A₁, A₂) and group IIb (A₃) of glycinin resulted in stiffer acid gels compared to the lines containing only β-conglycinin. These results confirmed that the ratio of glycinin/β-conglycinin has a significant effect on gel structure, with an increase in glycinin causing an increase in gel stiffness. The type of glycinin subunits also affected the aggregation behavior of soymilk.     

In Vitro Characterization and Mosquito (Aedes aegypti) Repellent Activity of Essential-Oils-Loaded Nanoemulsions

The nanoemulsions composed of citronella oil, hairy basil oil, and vetiver oil with mean droplet sizes ranging from 150 to 220 nm were prepared and investigated both in vitro and in vivo. Larger emulsion droplets (195–220 nm) shifted toward a smaller size (150–160 nm) after high-pressure homogenization and resulted in higher release rate. We proposed that thin films obtained from the nanoemulsions with smaller droplet size would have higher integrity, thus increasing the vaporization of essential oils and subsequently prolonging the mosquito repellant activity. The release rates were fitted with Avrami’s equations and n values were in the same range of 0.6 to 1.0, implying that the release of encapsulated limonene was controlled by the diffusion mechanism from the emulsion droplet. By using high-pressure homogenization together with optimum concentrations of 5% (w/w) hairy basil oil, 5% (w/w) vetiver oil (5%), and 10% (w/w) citronella oil could improve physical stability and prolong mosquito protection time to 4.7 h due to the combination of these three essential oils as well as small droplet size of nanoemulsion.     

<Emphasis Type="Italic">In Vivo</Emphasis> Assessment of Parenteral Formulations of Oligo(3-Hydroxybutyric Acid) Conjugates with the Model Compound Ibuprofen

Polymer-drug conjugates have gained significant attention as pro-drugs releasing an active substance as a result of enzymatic hydrolysis in physiological environment. In this study, a conjugate of 3-hydroxybutyric acid oligomers with a carboxylic acid group-bearing model drug (ibuprofen) was evaluated in vivo as a potential pro-drug for parenteral administration. Two different formulations, an oily solution and an o/w emulsion were prepared and administered intramuscularly (IM) to rabbits in a dose corresponding to 40 mg of ibuprofen/kilogramme. The concentration of ibuprofen in blood plasma was analysed by HPLC, following solid–phase extraction and using indometacin as internal standard (detection limit, 0.05 μg/ml). No significant differences in the pharmacokinetic parameters (C _max, T _max, AUC) were observed between the two tested formulations of the 3-hydroxybutyric acid conjugate. In comparison to the non-conjugated drug in oily solution, the relative bioavailability of ibuprofen conjugates from oily solution, and o/w emulsion was reduced to 17% and 10%, respectively. The 3-hydroxybutyric acid formulations released the active substance over a significantly extended period of time with ibuprofen still being detectable 24 h post-injection, whereas the free compound was almost completely eliminated as early as 6 h after administration. The conjugates remained in a muscle tissue for a prolonged time and can hence be considered as sustained release systems for carboxylic acid derivatives.     

The extraction,structure, and gelling properties of hybrid galactan from the red alga <Emphasis Type="Italic">Furcellaria lumbricalis</Emphasis> (Baltic Sea,Estonia)

The structure and composition of galactan from Furcellaria lumbricalis (furcellaran) were investigated in connection with rheological specificities, gel structure, and extraction conditions. The polysaccharide was characterized by ¹³C nuclear magnetic resonance (¹³C-NMR) and Fourier transform infrared spectroscopy, inductively coupled plasma-optical emission spectrometry, electrothermal atomization atomic absorption spectrometry, and gel permeation chromatography methods. The microstructure of polymer gels was studied using a cryofixation method in combination with freeze-drying and scanning electron microscopy (SEM) techniques. The undersulfated furcellaran backbone consists mainly of 3,6-anhydro-d-galactose (28.5–30.1%) and galactose residues, the latter being partly sulfated in positions 4 and 6, which give rise to some specific properties of the gel. Also, residues of 6-O-methyl-d-galactose as a minor component are found to be present. The water-extracted furcellaran with the average molecular weight about 290 kDa is rich in nitrogen, calcium, magnesium, and potassium, while the sodium content is rather low. The low sulfur content (5.3%) and ¹³C-NMR spectra refer to an undersulfated nature of this galactan. The extraction of seaweeds in low concentration alkaline solutions (instead of water) leads to a significant increase of the minimum size of the galactan particles and the value of gel strength (more than 12 times for Rb-containing gels). The properties of the gel are dependent on specific tentacle-like structure units present in furcellaran gels established by a high-resolution SEM.     

A Novel Transdermal Delivery System for the Anti-Inflammatory Lumiracoxib: Influence of Oleic Acid on <Emphasis Type="Italic">In Vitro</Emphasis> Percutaneous Absorption and <Emphasis Type="Italic">In Vivo</Emphasis> Potential Cutaneous Irritation

Transdermal delivery of non-steroidal anti-inflammatory drugs may be an interesting strategy for delivering these drugs to the diseased site, but it would be ineffective due to low skin permeability. We investigated whether oleic acid (OA), a lipid penetration enhancer in poloxamer gels named poloxamer-based delivery systems (PBDS), can improve lumiracoxib (LM) delivery to/through the skin. The LM partition coefficient (K) studies were carried out in order to evaluate the drug lipophilicity grade (K _{octanol/buffer}), showing values >1 which demonstrated its high lipophilicity. Both in vitro percutaneous absorption and skin retention studies of LM were measured in the presence or absence of OA (in different concentrations) in PBDS using porcine ear skin. The flux of in vitro percutaneous absorption and in vitro retention of LM in viable epidermis increased in the presence of 10.0% (w/w) OA in 25.0% (w/w) poloxamer gel. In vivo cutaneous irritation potential was carried out in rabbits showing that this formulation did not provide primary or cumulative cutaneous irritability in animal model. The results showed that 25.0% poloxamer gel containing 10.0% OA is potential transdermal delivery system for LM.     

<Emphasis Type="Italic">In Situ</Emphasis> Gelling Gelrite/Alginate Formulations as Vehicles for Ophthalmic Drug Delivery

The objective of this study was to develop an ion-activated in situ gelling vehicle for ophthalmic delivery of matrine. The rheological properties of polymer solutions, including Gelrite, alginate, and Gelrite/alginate solution, were evaluated. In addition, the effect of formulation characteristics on in vitro release and in vivo precorneal drug kinetic of matrine was investigated. It was found that the optimum concentration of Gelrite solution for the in situ gel-forming delivery systems was 0.3% (w/w) and that for alginate solution was 1.4% (w/w). The mixture of 0.2% Gelrite and 0.6% alginate solutions showed a significant enhancement in gel strength at physiological condition. On the basis of the in vitro results, the Gelrite formulations of matrine-containing alginate released the drug most slowly. For each tested polymer solution, the concentration of matrine in the precorneal area was higher than that of matrine-containing simulated tear fluid (STF) almost at each time point (p < 0.05). The area under the curve of formulation 16 (0.2%Gelrite/0.6%alginate) was 4.65 times greater than that of containing matrine STF. Both the in vitro release and in vivo pharmacological studies indicated that the Gelrite/alginate solution had the better ability to retain drug than the Gelrite or alginate solutions alone. The tested formulation was found to be almost non-irritant in the ocular irritancy test. The overall results of this study revealed that the Gelrite/alginate mixture can be used as an in situ gelling vehicle to enhance ocular retention.     

Rheological Behavior of Food Emulsions Mixed with Saliva: Effect of Oil Content, Salivary Protein Content, and Saliva Type

In this paper, we studied the effect of saliva on the rheological properties of β-lactoglobulin- and lysozyme-stabilized emulsions, prepared at pH = 6.7 in relation to variation of emulsions- and saliva-related parameters. The effect of oil–volume fraction (2.5% w/w to 10% w/w), salivary protein concentration (0.1 to 0.8 mg ml⁻¹), and the use of both stimulated and unstimulated saliva was investigated. Viscosity and storage modulus were measured before (η _emul and G′_emul, respectively) and after addition of saliva (η _mix and G′_mix). To better estimate the changes due to saliva-induced flocculation of the emulsions, the ratios η _mix/η _emul, G′_mix/G′_emul were calculated. In addition, tan δ (=the ratio of the loss and storage moduli) was investigated to evaluate the viscoelastic behavior of the emulsion/saliva mixtures. Increasing the oil–volume fraction and salivary protein concentration resulted in an increase in η _mix/η _emul and G′_mix/G′_emul, while a decrease in tan δ of the emulsion/saliva mixtures is occurring. When compared with unstimulated saliva, mixing β-lactoglobulin-stabilized emulsions with stimulated saliva led to a reduction in η _mix/η _emul and G′_mix/G′_emul, and an augment of tan δ at all measured deformations. In case of lysozyme-stabilized emulsions, the use of stimulated saliva increased G′_mix/G′_emul for γ < 3 when compared to unstimulated saliva. The effect of stimulated saliva on the η _mix/η _emul and tan δ in this mixture is similar to that of unstimulated saliva. These results indicate that the influence of stimulated saliva on the rheological parameters of emulsion/saliva mixtures largely depends on the type of emulsions. To conclude, our findings demonstrate that the rheological behavior of emulsions upon mixing with saliva is greatly affected by both saliva and emulsion properties.     

Hydrogels based on u.v.-crosslinked poly(ethylene oxide) – matrices for immobilization of <Emphasis Type="Italic">Candida boidinii</Emphasis> cells for xylitol production

Hydrogels based on high molecular weight poly(ethylene oxide) were synthesized by u.v.-irradiation of aqueous solutions in presence of the photoinitiator, (4-benzoylbenzyl)trimethylammonium chloride and different crosslinkers, poly(ethylene glycol), diacrylates and N,N′-methylenebisacrylamide. Candida boidinii cells were immobilized in these hydrogels and the gels were characterized in regards to gel fraction yield, degree of equilibrium swelling, shear storage and loss moduli. In addition, the number average molecular weight between crosslinks and the mesh size were estimated. The incorporated yeast cells considerably affected the viscoelastic properties of the gels. Immobilized C. boidinii cells were used for conversion of xylose to xylitol. Of the immobilized systems tested, only the system with poly(ethylene oxide) crosslinked with N,N′-methylenebisacrylamide exhibited xylitol production. The operational stability of this system was evaluated by seven repeated-batch runs performed in Erlenmeyer flasks in duration of 55 days. The progressive improvement of xylose consumption, up to 73.5%, stopped in the fifth cycle, after which it dropped to 42.7%. Although xylitol concentration never reached more than 4.2 g l⁻¹, xylitol was produced in each of the seven cycles. The cell leakage of 1.8 g l⁻¹ during the first 45 days, indicated very good stability of the system.     

A New Brassinolide-related Steroid in the Leaves of Thea sinensis

Microscopic and dynamic mechanical properties for mixed aqueous gels of agar and gelatin have been studied. The microscopic observation showed formation of micro granules in the gels under the phase-contrast visual field. The constituent was recognized as agar by metachroma tic staining using a microspectrophotometer. Dynamic moduli of the gels were measured from 0.01 to 200 Hz by phase difference and by resonance. A minimum E' value was obtained for the mixed gel at a volume fraction of agar of 0.6. E′ of all gels and E″ of mixed gels were frequency dependent above 30 Hz.     

Effect of Soy Soluble Polysaccharide on the Stability of Soy-Stabilised Emulsions During In Vitro Protein Digestion

This study investigated physicochemical properties of soy soluble polysaccharide (SSP) and pectinase-hydrolysed soy soluble polysaccharide (PH-SSP) from okara, the residue from soy milk production, and their influences when used as a fibre source in oil-in-water (o/w) emulsions. Although pectinase hydrolysed only the carbohydrate fraction in SSP, it resulted in the self-association of PH-SSP to the large-size aggregates. When PH-SSP was added to liquid emulsion containing 3.33% (w/v) rice bran oil and 3.75% (w/v) heated soy protein, it regulated the contents of protein in serum phase, sediment phase and at oil–water interface. The types and contents of soy proteins in the serum phase and sediment phase could be manipulated by pre-heating of soy proteins at 80 °C for 30 min and the addition of PH-SSP. The presence of PH-SSP (0–6% w/v) induced different distribution of proteins to the sediment phase and subsequent in vitro protein digestion in the emulsion. Overall, this study proposed the means to design the distributions of proteins in different phases of o/w emulsion for different degrees of oil release, emulsion stability and protein-polysaccharide coacervation during the course of in vitro peptic and tryptic digestion.     

Sustained Release of Amoxicillin from Ethyl Cellulose-Coated Amoxicillin/Chitosan–Cyclodextrin-Based Tablets

Sustained release mucoadhesive amoxicillin tablets with tolerance to acid degradation in the stomach were studied. The sustained-release tablets of amoxicillin were prepared from amoxicillin coated with ethyl cellulose (EC) and then formulated into tablets using chitosan (CS) or a mixture of CS and beta-cyclodextrin (CD) as the retard polymer. The effects of various (w/w) ratios of EC/amoxicillin, the particle sized of EC coated amoxicillin and the different (w/w) ratios of CS/CD for the retard polymer, on the amoxicillin release profile were investigated. The physicochemical properties of the EC coated amoxicillin particles and tablets were determined by scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry. The result showed that the release profiles of amoxicillin were greatly improved upon coating with EC, while the inclusion of CD to the CS retardant additionally prolonged the release of the drug slightly. Overall, a sustained release of amoxicillin was achieved using amoxicillin coated with EC at a (w/w) ratio of 1:1 and a particle size of 75–100 μm. Therefore, the tablet formulation of amoxicillin may be an advantageous alternative as an orally administered sustained-release formulation for the treatment of peptic ulcers.