Release Rate Of Theophylline Research Articles

In vitro release profiles of PLGA core-shell composite particles loaded with theophylline and budesonide

We investigated the effects of drug loading location, matrix material and shell thickness on the in vitro release of combinational drugs from core-shell PLGA (i.e., poly(lactic-co-glycolic acid)) particles. Budesonide and Theophylline were selected as highly hydrophobic and hydrophilic model drugs, respectively. The dual-capillary electrospray (ES) technique, operated at the cone-jet mode, was used to produce samples of drug-loaded core-shell composite particles with selected overall sizes, polymer materials, and shell thicknesses. Theophylline and Budesonide were loaded at different locations in a PLGA composite particle. This study illustrated how the aforementioned factors affect the release rates of Budesonide and Theophylline loaded in core-shell PLGA composites. We further identified that core-shell composite particles with both model drugs loaded in the core and with matrix PLGA polymers of low molecular weights and low LA/GA ratios are the best formulation for the sustained release of highly hydrophilic and hydrophobic active pharmaceutical ingredients from PLGA composite particles. The formulation strategy obtained in this study can be in principle generalized for biopharmaceutical applications in fixed-dose combination therapy.

Supercritical CO2 assisted liposomes formation: Optimization of the lipidic layer for an efficient hydrophilic drug loading

Liposomes are natural vesicles generally based on phosphatidylcholine (PC). The optimization of the lipid bilayer composition with the addition of little percentages of natural lipids is still at early stage due to the difficulties experienced by classical liposome formation processes, mainly, in reproducibility and encapsulation efficiency.Supercritical assisted liposome formation (SuperLip) has demonstrated that these limitations can be overcome. Therefore, in this work, this process has been tested to produce liposomes of controlled nanometric diameter and the effect of water solution flow rate on drug encapsulation efficiency was investigated. The addition of cholesterol (Chol) or phosphatidylethanolamine (PE) was also studied to gain the control on the release rate of the drug entrapped in liposomes. Theophylline was selected as the model hydrophilic drug.Using SuperLip process, PC/Chol and PC/PE liposomes were successfully produced with nanometric mean diameters down to 200nm. Optimization of both lipid composition and SuperLip operative parameters allowed to obtain theophylline encapsulation efficiencies up to 98%. Drug release kinetics were affected by liposome composition, in particular, the addiction of Chol and PE allowed to slow down theophylline release rate. These results confirmed the possibility of producing liposomes with a complex architecture of the lipid membrane using the SuperLip process.

OPTIMASI FORMULA MATRIKS KITOSAN DENGAN METILSELULOSA PADA PELEPASAN TERKENDALI SEDIAAN GRANUL TEOFILIN

The in vitro study was carried out on the release of active ingradient theophylline from granules prepared by moist granulation method. The granule matrix was prepared from the mixture of chitosan isolated from SwaIIo shrimp (Metapenaeus monoceros) (in accordance with the Protan Laboratories, Inc standard requirement) and methylceliuiose 1500 cps. The granules were filled into 850 mg capsules containing 200 mg theophylline. The maximum weight of chitosan and methylcellulose for each capsule was determined by factorial design 22.The result showed that, when the amount of chitosan was kept constant, an increase in the amount of methylcellulose will increase the release rate of theophylline from granules. The optimum weight of chitosan and methyIceIIuIose are 609.24 mg and 20.00 mg, respectively for one capsule.

The evaluation of physical properties of injection molded systems based on poly(ethylene oxide) (PEO)

The effect of product design parameters on the formation and properties of an injection molded solid dosage form consisting of poly(ethylene oxide)s (PEO) and two different active pharmaceutical ingredients (APIs) was studied. The product design parameters explored were melting temperature and the duration of melting, API loading degree and the molecular weight (Mw) of PEO. The solid form composition of the model APIs, theophylline and carbamazepine, was of specific interest, and its possible impact on the in vitro drug release behavior.Mw of PEO had the greatest impact on the release rate of both APIs. High Mw resulted in slower API release rate. Process temperature had two-fold effect with PEO 300,000g/mol. Firstly, higher process temperature transformed the crystalline part of the polymer into metastable folded form (more folded crystalline regions) and less into the more stable extended form (more extended crystalline regions), which lead to enhanced theophylline release rate. Secondly, the higher process temperature seemed to induce carbamazepine polymorphic transformation from p-monoclinic form III (carbamazepine (M)) into trigonal form II (carbamazepine (T)). The results indicated that the actual content of carbamazepine (T) affected drug release behavior more than the magnitude of transformation.

Predictive Evaluation of Heat Treatment Effect on Theophylline Release of Spray-Dried Pre-Gelatinised Glutinous Rice Starch Particles by near Infrared Spectroscopy

Starch is a natural polymeric with high chemical stability and no toxicity, so it is used widely as an additive in pharmaceutical manufacturing and the food industry. In this study, the effect of heat treatment on the controlled theophylline (TH) release rate of spray-dried pre-gelatinised glutinous rice starch (pGRS) was evaluated predictively by near infrared (NIR) spectroscopy. Spray-dried particles (SGRS) were obtained by spray-drying of TH ethanolic aqueous solution (TH: pGRS = 1: 1). The obtained SGRS was heat-treated to control drug release by chemical modification at 40–100°C. TH release test of the SGRS was performed to evaluate the drug release rate constant ( KH) in water at 37°C – body temperature. NIR spectra of heat-treated SGRS were recorded by diffuse reflectance NIR spectroscopy. The best calibration model consisted of five latent variables to predict KH and was determined by partial least squares (PLS) regression. Since the drug release profiles of TH from SGRS followed a Higuchi-type plot (diffusion-controlled sustained drug release), it was indicated that the rate-determining step of TH release is diffusion in polymeric matrices of SGRS. The KH of SGRS was evaluated based on Higuchi plots. It decreased with increasing temperature. X-ray diffraction and NIR results of SGRS suggested that TH recrystallised in SGRS after heat treatment. The relationship between actual and predicted KH values by our best PLS model based on NIR spectra gave a straight line with r2 = 0.990, with the slopes being close to 1. The KH of SGRS could be controlled by heat treatment. The KH could be predicted from NIR spectra and a chemometric method.

In vitro release testing of matrices based on starch–methyl methacrylate copolymers: Effect of tablet crushing force, dissolution medium pH and stirring rate

Direct-compressed matrix tablets were obtained from a variety of potato starch-methyl methacrylate copolymers(1) as sustained-release agents, using anhydrous theophylline as a model drug. The aim of this work was to investigate the influence of the copolymer type, the tablet crushing force and dissolution variables such as the pH of the dissolution medium and the agitation intensity on the in vitro drug release behaviour of such matrices. Commercial sustained-release theophylline products (Theo-Dur(®) 100mg, Theolair(®) 175 mg) were used as standards. Test formulations were compacted into tablets at three different crushing force ranges (70-80, 90-100 and 110-120 N) to examine the effect of this factor on the porous network and drug release kinetics. In vitro release experiments were conducted in a pH-changing medium (1.2-7.5) with basket rotation speeds in the range 25-100 r.p.m. to simulate the physiological conditions of the gastrointestinal tract. The release rate of theophylline was practically not affected by pH in the case of Theo-Dur(®) and HSMMA matrices. In contrast, Theolair(®) and CSMMA tablets demonstrated a biphasic drug release pattern, which appeared to be sensitive to the pH of the dissolution medium. An increase in the crushing force of the copolymer matrices was accompanied by a reduction of the matrix porosity, although the porous network depends markedly on the type of copolymer, having a strong influence on the drug release kinetics. Mathematical modelling of release data shows a Fickian diffusion or anomalous transport mechanism. Based on the similarity factor f2, FD-HSMMA, OD-CSMMA and FD-CSMMA at 90-100 N were selected for agitation studies. In general, all formulations showed an agitation speed-dependent release, with Theo-Dur(®) and FD-CSMMA matrices being the less susceptible to this factor.

Synthesis, pH sensitivity, and drug-release behavior of acrylic acid and polyhedral oligomeric silsesquioxane copolymer

pH-Sensitive organic–inorganic copolymers of hydrogels were developed as drug delivery systems (DDS) to improve the swelling behavior of polyacrylic acid (PAA). They were represented through FTIR, TGA and XRD characterization which revealed that the functional groups of methacryl-phenyl polyhedral oligomeric silsesquioxane (POSS) were successfully added to the acrylic acid (AA) molecular chains through radical solution polymerization. The DSC test results indicate that the addition of POSS could improve the thermal properties of the copolymers. The swelling properties at the pH range of 1.25–8.01 exhibited the pH sensitivity of POSS/AA copolymers (POSS-co-AA) and the lower swelling ratio in acidic conditions indicated that the DDS had low amount of release in SGF; this phenomenon suggested that the copolymer was available as DDS of theophylline. And it was proved by drug release curve and scanning electron microscopy. Since the addition of POSS reduced the release rate of theophylline and prolonged the release time of the drug, the concentration range of theophylline could remain low for an extended duration. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013

In vitro controlled release of theophylline from metal-drug complexes.

Two new metal-drug complexes constructed from non-toxic zinc and theophylline (TPL), an anti-asthmatic active drug, have been introduced into a release system based on matrices of hydroxypropylmethylcellulose (HPMC) and microcrystalline cellulose (MC). The release rate of TPL from the metal-drug complexes could be controlled by the amount of MC added, and the release mechanism changed from anomalous transport to Fickian diffusion.

Application of organogels as oral controlled release formulations of hydrophilic drugs

We previously demonstrated that organogels prepared from soybean oil using 12-hydroxy stearic acid as a gelator can slowly release ibuprofen, a model lipophilic drug. In this study, we investigated the applicability of organogels as controlled release formulations of hydrophilic drugs. The release rates of theophylline and ofloxacin, which are used as model hydrophilic drugs, were significantly slower than those of ibuprofen and antipyrine (model lipophilic drugs). Furthermore, no erosion was noted during drug release from organogels. Lipophilic drug molecules are released after diffusion in organogels because all molecules fully dissolve in the gel. On the other hand, hydrophilic drug molecules need to be dissolved before they diffuse in the organogel, prior to their release from the gel. Therefore, it is speculated that the release rates of hydrophilic drugs are slower than those of lipophilic drugs. To confirm the usefulness of organogels in controlled release formulations in vivo, organogels containing ibuprofen, ofloxacin, theophylline or antipyrine were intraduodenally administered to rats. All drugs used in this study were rapidly absorbed when administered in aqueous suspensions. In contrast, the drug concentrations in plasma after administration in organogels were lower; however, the lower concentrations of drugs sustained for 10 h after administration. With organogel administration, the mean residence time of drugs was longer than that with aqueous suspension administration. In conclusion, organogels are potential candidates for controlled release formulations of not only lipophilic drugs, but also hydrophilic drugs.

Formation and in-vitro evaluation of theophylline-loaded poly(methyl methacrylate) microspheres.

Theophylline-loaded poly(methyl methacrylate) (PMM) microspheres were prepared by the solvent evaporation method. Increasing the drug to polymer ratio increased both the mean particle size of the microspheres and the release rate. Polyethylene glycol (PEG) 4000 was used to improve the release rate of theophylline from the microspheres. No marked effect was observed on particle size distribution of the microspheres as a function of PEG concentration but there was a pronounced effect on drug release. The different particle sizes of microspheres prepared from the same drug to polymer ratio showed no significant difference in drug content, indicating that the ratio between theophylline and PMM remained practically constant regardless of the size of microspheres. Release characteristics of the microspheres were influenced by drug to polymer ratio, the amount of PEG incorporated and the particle size of microspheres. The release rate was slightly higher in simulated gastric fluid than in simulated intestinal fluid. The release profiles of the drug were modified by mixing microspheres of different formulations in different ratios.

Release kinetics of sparingly soluble drugs from ethyl cellulose-walled microcapsules: theophylline microcapsules.

Release rates of theophylline from ethyl cellulose-coated microcapsules were measured as a function of wall thickness and core particle size. The kinetic data conformed with first order release and also the Higuchi matrix model. However, application of the differential rate treatment, hitherto applied only to drug matrix dispersions, showed that release from the microcapsules definitely followed the first order equation. For the purpose of confirming that the release process was membrane-controlled, the experimental rate constants were transformed into effective permeability constants (P1) with the aid of the microcapsule dimensional parameters needed in the relevant equations and compared with the permeability constant (P) of theophylline measured experimentally using planar ethyl cellulose membranes. P1 values decreased linearly to a moderate extent with wall thickness, probably due to decrease in porosity during wall-formation. P1 values of the thicker-walled microcapsules were found to be of the same order as the membrane P value, supporting a release mechanism of membrane control under non-steady state conditions.

In vivo evaluation of two new sustained release formulations elaborated by one-step melt granulation: Level A in vitro–in vivo correlation

The objective of this study was to evaluate in vivo two sustained release formulations elaborated by a one-step melt granulation method using theophylline as model drug. Both formulations presented differences in the in vitro release profile due to the hydrophilic or lipophilic nature of the binder employed (PEG 6000 or glycerol monostearate). The formulations were administered to Beagle dogs, and plasma levels were compared. Both formulations provided a sustained plasma concentration profile after oral administration to dogs. Significant differences ( p < 0.05) in the plasma concentration–time curves between the two formulations were found, with higher C max (6.05 ± 2.00 vs. 2.55 ± 0.82 μg/mL), higher AUC 0–∞ (70.24 ± 16.10 vs. 33.00 ± 8.96 h μg/mL) and delayed T max (6.00 ± 2.12 vs. 3.17 ± 0.98 h) for the formulation containing PEG 6000. Absolute bioavailability of theophylline was 96% and 46% for the formulations containing PEG 6000 and glycerol monostearate, respectively. These results are consistent with those obtained in vitro, with slower release rate of theophylline from tablets elaborated with glycerol monostearate than that obtained with tablets elaborated with PEG 6000. Moreover, the formulation containing PEG 6000 provided a plasma concentration–time profile similar to that obtained with the marketed formulation Theo-Dur®. A very good Level A IVIVC was observed between dissolution and absorption profiles of the drug from both test formulations. Our results showed that one-step melt granulation in a high shear mixer allows for an easy modulation of the release profile and, consequently, of the plasma level profile of the drug by selecting the type of binder used.

Properties of melt extruded enteric matrix pellets

The objective of this study was to investigate the properties of enteric matrix pellets that were prepared by hot-melt extrusion in a one-step, continuous process. Five polymers (Eudragit® L100-55, L100 and S100, Aqoat® grades LF and HF) were investigated as possible matrix formers, and pellets prepared with Eudragit® S100 demonstrated superior gastric protection and acceptable processibility. Extruded pellets containing Eudragit® S100 and up to 40% theophylline released less than 10% drug over 2 h in acid, however, the processibility and yields were compromised by the high amounts of the non-melting drug material in the formulation. Efficient plasticization of Eudragit® S100 was necessary to reduce the polymer’s glass transition temperature and melt viscosity. Five compounds including triethyl citrate, methylparaben, polyethylene glycol 8000, citric acid monohydrate and acetyltributyl citrate were investigated in terms of plasticization efficiency and preservation of the delayed drug release properties. The aqueous solubility of the plasticizer and its plasticization efficiency impacted the drug release rate from the matrix pellets. The use of water-soluble plasticizers resulted in a loss of gastric protection, whereas low drug release rates in acid were found for pellets containing insoluble plasticizers or no plasticizer, independent of the extent of Eudragit® S100 plasticization. The release rate of theophylline in buffer pH 7.4 was faster for pellets that were prepared with efficient plasticizers. The microstructure and solid-state properties of plasticized pellets were further investigated by scanning electron microscopy and powder X-ray diffraction. Pellets prepared with efficient plasticizers (TEC, methylparaben, PEG 8000) exhibited matrices of low porosity, and the drug was homogeneously dispersed in its original polymorphic form. Pellets containing ATBC or citric acid monohydrate had to be extruded at elevated temperature and showed physical instabilities in the form of recrystallization at room temperature. Enteric matrix pellets with a diameter below 1 mm and containing 30% theophylline could be successfully prepared by hot-melt extrusion when Eudragit® S100 plasticized with either TEC or methylparaben was employed as the matrix material.

Optimization and Development of Swellable Controlled Porosity Osmotic Pump Tablet for Theophylline

Purpose: To develop swellable controlled porosity osmotic pump tablet of theophylline and to define the formulation and process variables responsible for drug release by applying statistical optimizationtechnique.Methods: Formulations were prepared based on Taguchi Orthogonal Array design and Fraction Factorial design for core and coating, respectively. The tablets were prepared by direct compression and wet granulation methods; spray coated with ethyl cellulose solution containing varying amounts ofPEG 400 and plasdone. Drug release from the osmotic drug delivery system was studied using USP Type I paddle type apparatus. The membrane morphology of the delivery system was determined byscanning electron microscopy (SEM).Results: Optimization results indicated that the release rate of theophylline from the swellable controlled porosity osmotic pump tablet is directly proportional to the levels of osmotic agent, solubilizing agent andpore former in the tablet core and the membrane, respectively. SEM showed the formation of pores in the membrane through which drug release occurred. The best formulation showed 98.2 % drug releaseand complied with USP requirements.Conclusion: The results confirmed that the factors responsible for drug release were osmotic agents (core) and pore former (membrane). Also, the preparation of swellable controlled porosity osmotic pumptablet was facilitated by coating the core tablet with pore forming agent, thus eliminating the need for the more expensive laser drilling.

Influence of an Acrylic Polymer Blend on the Physical Stability of Film-Coated Theophylline Pellets

The purpose of this study was to investigate the physical stability of a coating system consisting of a blend of two sustained release acrylic polymers and its influence on the drug release rate of theophylline from coated pellets. The properties of both free films and theophylline pellets coated with the polymer blend were investigated, and the miscibility was determined via differential scanning calorimetry. Eudragit RS 30 D was plasticized by the addition of Eudragit NE 30 D, and the predicted glass transition temperature (T(g)) of the blend was similar to the experimental values. Sprayed films composed of a blend of Eudragit NE 30 D/Eudragit RS 30 D (1:1) showed a water vapor permeability six times greater than films containing only Eudragit NE 30 D. The presence of quaternary ammonium functional groups from the RS 30 D polymer increased the swellability of the films. The films prepared from the blend exhibited stable permeability values when stored for 1 month at both 25 degrees C and 40 degrees C, while the films which were composed of only Eudragit NE 30 D showed a statistically significant decrease in this parameter when stored under the same conditions. Eudragit NE 30 D/Eudragit RS 30 D (1:1)-sprayed films decreased in elongation from 180% to 40% after storage at 40 degrees C for 1 month, while those stored at 25 degrees C showed no change in elongation. In coated pellets, the addition of Eudragit RS 30 D to the Eudragit NE 30 D increased the theophylline release rate, and the pellets were stable when stored at 25 degrees C for a period of up to 3 months due to maintenance of the physico-mechanical properties of the film. Pellets stored at 40 degrees C exhibited a decrease in drug release rate over time as a result of changes in film physico-mechanical properties which were attributed to further coalescence and densification of the polymer. When the storage temperature was above the T(g) of the composite, instabilities in both drug release rate and physical properties were evident. Stabilization in drug release rate from coated pellets could be correlated with the physico-mechanical stability of the film formulation when stored at temperatures below the T(g) of the polymer.

Development and characterization of extended release Kollidon ® SR mini-matrices prepared by hot-melt extrusion

Kollidon ® SR as a drug carrier and two model drugs with two different melting points, ibuprofen and theophylline, were studied by hot-melt extrusion. Powder mixtures containing Kollidon ® SR were extruded using a twin-screw extruder at temperatures 70 and 80 °C for ibuprofen and 80 and 90 °C for theophylline. The glass transition temperature ( T g) and maximum torque were inversely related to ibuprofen concentrations, indicating its plasticizing effect. The results of differential scanning calorimetry (DSC) and X-ray diffraction analysis showed that ibuprofen remained in an amorphous or dissolved state in the extrudates containing drug up to 35%, whereas theophylline was dispersed in the polymer matrix. The increase in amounts of ibuprofen or theophylline in the hot-melt extrudates resulted in the increase in the drug release rates. Theophylline release rate in hot-melt extruded matrices decreased as the extrusion temperature increased. In contrast, a higher processing temperature caused the higher ibuprofen release. This was a clear indication of the plasticizing effect of ibuprofen on Kollidon ® SR and a result from water uptake. Theophylline release rate from hot-melt extrudates decreased with increasing triethyl citrate (TEC) level because of the formation of a denser matrix. By adding of Klucel ® LF as a water-soluble additive to the hot-melt extruded matrices, an increase in ibuprofen and theophylline release rates was obtained.

Poly(MAA-co-AN) hydrogels with improved mechanical properties for theophylline controlled delivery

A hydrophobically improved copolymer hydrogel was constructed and developed based on methacrylic acid (MAA) and acrylonitrile (AN) monomers. The swelling investigations indicated that the hydrogels were highly sensitive to the pH and ionic strength of the surrounding environment. The swelling ratios of the gels in stimulated intestinal fluids (SIF, pH 7.4) were higher than those in stimulated gastric fluids (SGF, pH 1.4), and followed a non-Fickian and a Fickian diffusion mechanism, respectively. The results match well with scanning electron microscopy observations showing that mesh sizes in hydrogels in SGF are larger and more patulous than in SIF. It is believed that the phenomena are concerned with the electrostatic repulsion originating from the formation and dissociation of carboxyl groups, as well as a charge screening effect of the cations leading to the reduction of osmotic pressure. A dynamic mechanical analyzer revealed that the addition of hydrophobic AN units notably improved the compression mechanical properties of the control sample. With an increase in AN concentrations, the ability for the copolymers to resist compression deformation enhanced in distilled water and the compression strains have almost the same values in SIF environments. Differential scanning calorimetry was used to analyze the state of water and to determine the amounts of freezing and non-freezing water. The controlled release examination based on the theophylline model drug showed that the release rate in distilled water was faster than that in SIF or SGF. The introduction of the hydrophobic AN decreased the theophylline release rates in both SIF and SGF, and the release rate variation in SIF was notably larger than that in SGF. The drug release behavior of the AN-modified P(MAA-co-AN) copolymer hydrogel deviates from the Fickian diffusion control mechanism. This hydrogel is expected to be used as an excellent material in oral drug controlled release.

Wax-based sustained release matrix pellets prepared by a novel freeze pelletization technique: II. In vitro drug release studies and release mechanisms

A novel freeze pelletization technique was evaluated for the preparation of wax-based sustained release matrix pellets. Pellets containing water-soluble drugs were successfully prepared using a variety of waxes. The drug release significantly depended on the wax type used and the aqueous drug solubility. The drug release decreased as the hydrophobicity of wax increased and the drug release increased as the aqueous drug solubility increased. In glyceryl monostearate (GMS) pellets, drug release rate decreased as the loading of theophylline increased. On the contrary, the release rate increased as the drug loading of diltiazem HCl increased in Precirol pellets. Theophylline at low drug loads existed in a dissolved state in GMS pellets and the release followed desorption kinetics. At higher loads, theophylline existed in a crystalline state and the release followed dissolution-controlled constant release for all the waxes studied. However, with the addition of increasing amounts of Brij 76, theophylline release rate increased and the release mechanism shifted to diffusion-controlled square root time kinetics. But the release of diltiazem HCl from Precirol pellets at all drug loads, followed diffusion-controlled square root time kinetics. Therefore, pellets capable of providing a variety of release profiles for different drugs can be prepared using this freeze pelletization technique by suitably modifying the pellet forming matrix compositions.

Influence of Fumed Silicon Dioxide on the Stabilization of Eudragit®RS/RL 30 D Film-Coated Theophylline Pellets

The objective of this study was to investigate the influence of various grades of fumed silicon dioxide on the drug release rate and physical aging of theophylline pellets coated with Eudragit® RS 30 D and RL 30 D. Free films were assessed for both physicomechanical properties and water vapor permeability with respect to time and storage conditions. The release rate of theophylline was influenced by the physical properties of the silicon dioxide employed. As the particle size of the silica dioxide decreased, there was an increase in dispersion viscosity, as well as a decrease in the theophylline release rate from the coated pellets. Films prepared from formulas containing Aeroperl® 300 had twice the water vapor transmission rate of films prepared from formulas containing Aerosil® 200 VV and Cab-O-Sil® M-5P and showed consistent moisture permeability values during storage for up to 1 month at 25°C/0% relative humidity (RH). Scanning electron microscopy (SEM) imaging of pellets coated with a formulation containing Aerosil® 200 VV or Cab-O-Sil® M-5P demonstrated film structures that were homogenous, while those coated with a formulation containing Aeroperl® 300 produced heterogeneous films with large particles of the excipient present within the polymeric matrix of the film. Stability in the drug release rate exhibited by pellets coated with a formulation containing Eudragit® RS 30 D, 15% triethyl citrate (TEC), and 30% Aeroperl® 300 was attributed to the stabilization of the moisture vapor transmission rate of the acrylic films. Increasing the concentration of Aeroperl® 300 in the coating formulation increased the theophylline release rate from coated pellets.

Incidence of drying on microstructure and drug release profiles from tablets of MCC–lactose–Carbopol ® and MCC–dicalcium phosphate–Carbopol ® pellets

The influence of intragranular excipients (lactose or dicalcium phosphate) and the drying procedure and conditions (oven-drying and freeze-drying after freezing at −30 or −196 °C) on the properties of tablets of MCC–Carbopol ® pellets was evaluated. The drying procedure caused remarkable differences in pellet size and porosity (freeze-dried pellets were 3-fold more porous than those oven dried). Theophylline release from pellets was completed in less than 30 min and followed first-order kinetics, with a rate closely related to the intragranular porosity. The total porosity of the tablets (5–10%) was conditioned by the compression force (10–20 N), the drying procedure applied to the pellets and the coexcipient nature. Their intergranular porosity ranged inversely to the initial porosity of pellets due to the greater deformability of the most porous ones. A wide range of theophylline release rates were achieved depending on the drying procedure; tablets prepared from freeze-dried pellets sustained the release for 3 h. Most profiles showed a bimodal kinetics with an initial zero-order release (while the tablets did not completely disintegrate) that changed, after a certain time, to a first-order kinetics. The intergranular porosity determined drug release rate up to disintegration. Then, the release kinetics became first-order and the rate constant, which was conditioned by the intragranular porosity, showed a complex dependence on the drying procedure, the compression force, and the nature of coexcipient. In sum, the modulation of drug release profiles from tablets of MCC–Carbopol ® pellets through an adequate control of the effects of the coexcipient nature, the drying procedure of pellets, and the compression force on the inter- and intragranular porosity opens interesting possibilities to control the release of hydrosoluble drugs.