Release Of Theophylline Research Articles

Tuning bio-aerogel properties. Part 3: Exploring silica-pectin composite aerogels for drug delivery

The release of the model drug theophylline from silica-pectin aerogels was investigated. The composite aerogels were prepared via impregnation of pectin alcogels with silica sol, followed by in situ silica gelation and drying with supercritical CO2. The structural and physico-chemical properties of the aerogels were tuned via the preparation conditions (type of silica sol, calcium crosslinking of pectin or not). Theophylline was loaded via impregnation and its release into simulated gastric fluid was studied during 1 h followed by release into simulated intestinal fluid. The swelling, mass loss and theophylline release behavior of the composites were analyzed and correlated with material properties. It followed that only aerogels prepared with calcium-crosslinked pectin and polyethoxydisiloxane were stable in aqueous systems, exhibiting a slow theophylline release governed by near-Fickian diffusion.

N-Hydroxyalkanamide Based Organo/hydrogels as Novel Scaffolds for pH-Dependent Metronidazole and Theophylline Release.

The traditional delivery of metronidazole and theophylline presents challenges like bitter taste, variable absorption, and side effects. However, gel-based systems offer advantages including enhanced targeted drug delivery, minimized side effects, and improved patient compliance, effectively addressing these challenges. Consequently, a cost-effective synthesis of N-hydroxyalkanamide gelators with varying alkyl chain lengths was achieved in a single-step reaction procedure. These gelators formed self-assembled aggregates in DMSO/water solvent system, resulting in organo/hydrogels at a minimum gelation concentration of 1.5 % w/v. Subsequently, metronidazole and theophylline were encapsulated within the gel core and released through gel-to-sol transition triggered by pH variation at 37 °C, while maintaining the structural-activity relationship. UV-vis spectroscopy was employed to observe the drug release behavior. Furthermore, in vitro cytotoxicity assays revealed cytotoxic effects against A549 lung adenocarcinoma cells, indicating anti-proliferative activity against human lung cancer cells. Specifically, the gel containing theophylline (16HAD+Th) exhibited cytotoxicity on cancerous A549 cells with IC50 values of 19.23±0.6 μg/mL, followed by the gel containing metronidazole (16HAD+Mz) with IC50 values of 23.75±0.7 μg/mL. Moreover, the system demonstrated comparable antibacterial activity against both gram-negative (E. coli) and gram-positive bacteria (S. aureus).

Agarose as a tunable platform for oral drug delivery: Controlled release of a highly soluble drug, theophylline, within a sequentially-changing-pH medium

The purpose of this study was to expand the use of freeze-dried agarose-based systems for the oral controlled release of highly water-soluble drugs. Three additives (Eudragit S-100 and RL-PO and Labrafac) were included within these systems together with Theophylline. The release of this drug from the rehydrated systems was evaluated in deionized water and in a sequentially-changing-pH medium that simulated the conditions under oral administration. Considering the results obtained in the preliminary release test in water, only the Eudragit-containing compositions were further characterized. The theophylline release in a sequentially-changing-pH medium showed two different patterns that mainly depend on the additive nature: those systems containing Eudragit S-100 showed a similar behaviour to that observed in the absence of additives while the presence of Eudragit RL-PO yields a progressive and pH-independent release. Agarose-based systems were capable of accommodating additives that allows tailoring a controlled release of theophylline, a highly soluble drug.

Effect of Hydration Forms and Polymer Grades on Theophylline Controlled-Release Tablet: An Assessment and Evaluation.

Drug release from controlled release delivery systems is influenced by various factors, including the polymer's grade and the drug's hydration form. This study aimed to investigate the impact of these factors on the controlled release of theophylline (THN). This research compares the monohydrate form found in branded products with the anhydrous form in generic equivalents, each formulated with different polymer grades. Quality control assessment was conducted alongside in vitro evaluation, complemented by various analytical techniques such as X-ray diffraction (XRD) and scanning electron microscopy (SEM). Additionally, thermal analyses using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were employed. Quality control assessments demonstrated that the generic tablets exhibited lower average weight and resistance force compared to the branded ones. In vitro tests revealed that generic tablets released contents within 120 min, compared to 720 min for the branded counterpart. Characterization using XRD and SEM identified disparities in crystallinity and particle distribution between the three samples. Additionally, the thermal analysis indicated consistent endothermic peaks across all samples, albeit with minor variations in heat flow and decomposition temperatures between the two products. This study demonstrated that variations in polymer grade and hydration form significantly impact THN release.

Potentials of Sterculia tragacantha Lindl seed husk gum as a release modifier in matrix tablet formulation

Natural gums have been utilized severally in the design of matrix tablets, either in their native or modified forms. The primary objective of this work was the extraction, characterization and utilization of the seed husk gum from Sterculia tragacantha Lindl as a release modifier in theophylline matrix tablets. Gum was extracted from the fresh seed husk of Sterculia tragacantha and tablet formulated via wet granulation. Drug-polymer compatibility was determined by FTIR and DSC while formulated tablets were evaluated for their in vitro dissolution release profile in two media, simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) and compared with a commercial brand. Extracted gum powder presented a poor flow which improved on granulation, had a better swelling index and water holding capacity than tragacanth gum. Formulated tablets passed standard tablets test and sustained theophylline release up to 90.97 % and 88.09 % in SGF and SIF respectively at the twelfth hour. Drug release kinetics was by zero order in SGF via non-fickian diffusion. S. tragacantha seed husk gum presented a promising potential as a release retarding agent.

Rational design of keratin nanoparticles utilizing diverse hair protein fractions for controlled drug release

BackgroundHair keratin exhibits potential as a nanocarrier material owing to its biocompatibility, biodegradability, and adaptability. However, conventional extraction methods yield mixtures of KIFs and KAPs. While prior research has delved into keratin nanoparticles, none have specifically investigated those derived from distinct keratin subgroups. MethodsTo address this gap, we assessed the particle size, zeta potential, secondary structure, and drug release properties of spray-dried keratin nanoparticles generated from diverse KAPs/KIFs mixtures. Significant FindingsOur findings reveal that KAPs/KIFs ratios directly impact keratin nanoparticles’ protein structures and properties. When a higher proportion of KAPs is involved, there is a greater repulsive force between particles, reducing their tendency to aggregate. Conversely, increased KIFs content results in smaller particles and reduced electrostatic repulsion, potentially enhancing Theophylline release. Therefore, fine-tuning drug release behavior by adjusting KAPs and KIFs ratios while considering environmental pH values is critical to address aggregation problems while maximizing drug loading and encapsulation efficiency. These results underscore the importance of controlled keratin composition for developing reliable, keratin-based biomaterials tailored for diverse biomedical applications.

Combinatorial 3D printed dosage forms for a two-step and controlled drug release

Fused deposition modeling (FDM) and selective laser sintering (SLS) are two of the most employed additive manufacturing (AM) techniques within the pharmaceutical research field. Despite the numerous advantages of different AM methods, their respective drawbacks have yet to be fully addressed, and therefore combinatorial systems are starting to emerge. In the present study, hybrid systems comprising SLS inserts and a two-compartment FDM shell are developed to achieve controlled release of the model drug theophylline. Via the use of SLS a partial amorphization of the drug is demonstrated, which can be advantageous in the case of poorly soluble drugs, and it is shown that sintering parameters can regulate the dosage and release kinetics of the drug from the inserts. Furthermore, via different combinations of inserts within the FDM-printed shell, various drug release patterns, such as a two-step or prolonged release, can be achieved. The study serves as a proof of concept, highlighting the advantages of combining two AM techniques, both to overcome their respective shortcomings and to develop modular and highly tunable drug delivery devices.

Starch Alcogels, Aerogels, and Aerogel-like Xerogels: Adsorption and Release of Theophylline

Starch is one of the most abundant and biodegradable natural polysaccharides; it has been widely used in pharmaceutics in tablets, as a disintegrant, or as a porous carrier. In this work, starches in different forms─alcogels, aerogels, and low-vacuum-dried materials (named xerogels)─were designed and tested as carriers of theophylline. The influence of the starch amylose/amylopectin ratio, concentration in solution, retrogradation time, and drying method (supercritical CO2 drying for aerogels, low-vacuum drying for xerogels) on materials’ density, specific surface area, and morphology was investigated. The precursors before drying were starch alcogels made by water-to-ethanol exchange in retrograded hydrogels. Starch alcogels were loaded with theophylline via impregnation. Loading capacities and efficiencies of alcogels, aerogels, and xerogels were determined, and release of the drug from xerogels and aerogels was evaluated. Two remarkable phenomena were obtained: (1) The low-vacuum drying method resulted in starch aerogel-like materials; i.e., xerogels with low densities and specific surface areas above 100 m2/g. (2) Starch alcogels adsorbed theophylline from ethanol resulting in loading efficiency as high as 250%. The results obtained show a new pathway in making aerogel-like polysaccharide materials without drying in supercritical conditions for potential use as drug carriers.

Sustainable 3D printing of oral films with tunable characteristics using CMC-based inks from durian rind wastes

With the growing interest in environmentally friendly and personalized medicines, new concept for combining three-dimensional printing (3DP) with natural-based biomaterials derived from agro-food wastes has emerged. This approach provides sustainable solutions for agricultural waste management and potential for developing of novel pharmaceutical products with tunable characteristics. This work demonstrated the feasibility of fabricating personalized theophylline films with four different structures (Full, Grid, Star, and Hilbert) using syringe extrusion 3DP and carboxymethyl cellulose (CMC) derived from durian rind wastes. Our findings suggested that all the CMC-based inks with shear thinning properties capable of being extruded smoothly through a small nozzle could potentially be used to fabricate the films with various complex printing patterns and high structural fidelity. The results also demonstrated that the film characteristics and release profiles could be easily modified by simply changing the slicing parameters (e.g., infill density and printing pattern). Amongst all formulations, Grid film, which was 3D-printed with 40 % infill and a grid pattern, demonstrated a highly porous structure with high total pore volume. The voids between printing layers in Grid film increased theophylline release (up to 90 % in 45 min) through improved wetting and water penetration. All findings in this study provide significant insight into how to modify film characteristics simply by digitally changing the printing pattern in slicer software without creating a new CAD model. This approach could help to simplify the 3DP process so that non-specialist users can easily implement it in community pharmacies or hospital on demand.

Natural rubber blends for floating theophylline beads

Natural rubber (NR)'s value has become increasingly important for human applications. This study prepared NR beads as floating drug delivery system by dripping NR latex into hardening solution to obtain spherical beads. Theophylline was loaded as a model drug. NR latex formed into harden beads suddenly after dripping droplets in acidic medium. These NR beads floated instantly and buoyant in HCl buffer for over 8 h with prolonged theophylline release. Their morphologies, crystallinity and thermal properties were observed using microscope, X-ray diffractometer, and thermogravimetry, respectively. Addition of 100 phr sodium bicarbonate increased drug release owing to liberation of carbon dioxide promoting porous NR matrix. Composite of 50 and 200 phr shellac in NR beads floated in HCl buffer for over 12 h. Moreover, 200 phr shellac efficiently retarded release of theophylline from NR composite beads (lower than 10 % in 8 h), whereby promoting theophylline release in phosphate buffer (pH 6.8) (approximately 80 % in 8 h). NR-shellac beads had greater water sorption (2.5 times) and erosion (4.9 times) in phosphate buffer than in HCl buffer. Thus, NR beads exhibited desirable attributes as floating drug delivery system. Both sodium bicarbonate and shellac modified matrix properties and drug release of NR beads.

The Effect of Biorelevant Hydrodynamic Conditions on Drug Dissolution from Extended-Release Tablets in the Dynamic Colon Model.

The in vitro release of theophylline from an extended-release dosage form was studied under different hydrodynamic conditions in a United States Pharmacopoeial (USP) dissolution system II and a bespoke in vitro tubular model of the human colon, the Dynamic Colon Model (DCM). Five biorelevant motility patterns extracted from in vivo data were applied to the DCM, mimicking the human proximal colon under baseline conditions and following stimulation using polyethylene glycol or maltose; these represent the lower and upper bounds of motility normally expected in vivo. In the USPII, tablet dissolution was affected by changing hydrodynamic conditions at different agitation speeds of 25, 50 and 100 rpm. Applying different motility patterns in the DCM affected the dissolution profiles produced, with theophylline release at 24 h ranging from 56.74 ± 2.00% (baseline) to 96.74 ± 9.63% (maltose-stimulated). The concentration profiles of theophylline were markedly localized when measured at different segments of the DCM tube, highlighting the importance of a segmented lumen in intestine models and in generating spatial information to support simple temporal dissolution profiles. The results suggested that the shear stresses invoked by the unstimulated, healthy adult human colon may be lower than those in the USPII at 25 rpm and thus insufficient to achieve total release of a therapeutic compound from a hydroxyethyl cellulose matrix. When operated under stimulated conditions, drug release in the DCM was between that achieved at 25 and 50 rpm in the USPII.

STUDI PELEPASAN TEOFILIN DARI CANGKANG KAPSUL ALGINAT-KITOSAN MENGGUNAKAN TRIPOLIFOSFAT SEBAGAI CROSSLINKER

The modified formulation provides a fairly effective way to overcome the problem of bioavailability and results in increasing drug reactions and minimizing fluctuations in blood levels during release. The crosslinker in this study is sodium tripolyphosphate (Na-TPP) which is considered the best binding agent and can produce prolonged drug release. The purpose of this study was to determine the profile of theophylline release from the capsule shell of the alginate-chitosan matrix combination using the crosslink method. The capsule shell was made with the ratio of the percentage of alginate ; chitosan; The TPP are F1 (2%; 2%; 4%) and F2 (4%; 2%; 4%). The difference in percentage is intended to determine the ratio of the most optimal levels of releasing theophylline. The results obtained showed that theophylline capsules from formulas F1 and F2 could release the drug slowly and for a long time to the artificial intestinal fluid pH 7.4 for 8 hours for formula F1 and for 12 hours for formula F2 with a cumulative percentage of release of 99.75%.

Formulation and evaluation of theophylline sustained release matrix tablets using synthetic polymers

The aim of present work was to develop theophylline sustained release tablets which could improve patient compliance towards the effective management of asthma The polymers, HPMC (Hydroxy propyl methyl cellulose) K4M, HPMC K100M, Eudragit, Chitosan in blending and granulation stage of processing and evaluate their physico-chemical properties. The precompression limits of the powder blends used for the preparation of sustained-release tablets were in an acceptable range of pharmacopeial specification with excellent flow and good compressibility. Wet granulation method prepared tablets using different grades of polymers HPMC K100, HPMC K4M, Eudragit, Chitosan. The active ingredient, release retardants, diluents, fraction of polymer are mixed to make wet mass for granulation. The in- vitro release was prolonged to 12 hours using HPMC K4M, HPMC K100M, Chitosan, Eudragit. F9 formulation prolonged the theophylline release in 12 hours. The effect of polymer on drug release was studied. Thus, sustained release matrix tablets can promise better patient compliance through reduction in over-all dose and dosage regimen, which can be of excessive support to treat chronic disease.

Controlled release of theophylline from ethyl cellulose coated PVA/NaCMC-theophylline microspheres

Theophylline (TF) was preferably used for the treatment of asthma and chronic obstructive pulmonary diseases. However, it has a limited therapeutic range. So the controlled release of theophylline is required. In this study, TF was encapsulated with poly (vinyl alcohol) (PVA) and sodium carboxy methyl cellulose (NaCMC) polymers by using ionic gelation and liquid ripening method and iron III chloride (FeCl3) was used as crosslinking agent. Prepared microspheres were characterized and also defined by equilibrium swelling values and release profiles. Microspheres, in which the most suitable release conditions were determined, coated with EC and drug release studies were carried out.

Tuning bio-aerogel properties for controlling drug delivery. Part 2: Cellulose-pectin composite aerogels

The release of the model drug theophylline from cellulose-pectin composite aerogels was investigated. Cellulose and pectin formed an interpenetrated network, and the goal was to study and understand the influence of each component and its solubility in simulated gastric and intestinal fluids on the kinetics of release. Cellulose was dissolved, coagulated in water, followed by impregnation with pectin solution, crosslinking of pectin with calcium (in some cases this step was omitted), solvent exchange and supercritical CO2 drying. Theophylline was loaded via impregnation and its release into simulated gastric fluid was monitored for 1h followed by release into simulated intestinal fluid. The properties of the composite aerogels were varied via the cellulose and pectin concentrations as well as the calcium content in the precursor solutions. The release kinetics was correlated with aerogel specific surface area, bulk density as well as network swelling and erosion. The Korsmeyer-Peppas model was employed to identify the dominant release mechanisms during the various stages of the release.

Formulation, Characterization, and In Vitro Drug Release Study of β-Cyclodextrin-Based Smart Hydrogels.

In this study, novel pH-responsive polymeric β-cyclodextrin-graft-poly(acrylic acid/itaconic acid) hydrogels were fabricated by the free radical polymerization technique. Various concentrations of β-cyclodextrin, acrylic acid, and itaconic acid were crosslinked by ethylene glycol dimethacrylate in the presence of ammonium persulfate. The crosslinked hydrogels were used for the controlled delivery of theophylline. Loading of theophylline was conducted by the absorption and diffusion method. The fabricated network of hydrogel was evaluated by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray diffractometry (XRD), and scanning electron microscopy (SEM). The crosslinking among hydrogel contents and drug loading by the fabricated hydrogel were confirmed by FTIR analysis, while TGA indicated a high thermal stability of the prepared hydrogel as compared to pure β-cyclodextrin and itaconic acid. The high thermal stability of the developed hydrogel indicated an increase in the thermal stability of β-cyclodextrin and itaconic acid after crosslinking. Similarly, a decrease in crystallinity of β-cyclodextrin and itaconic acid was observed after crosslinking, as evaluated by XRD analysis. SEM revealed an irregular and hard surface of the prepared hydrogel, which may be correlated with strong crosslinking among hydrogel contents. Crosslinked insoluble and uncrosslinked soluble fractions of hydrogel were evaluated by sol–gel analysis. An increase in gel fraction was seen with the increase in compositions of hydrogel contents, while a decrease in sol fraction was observed. Dynamic swelling and dissolution studies were performed in three various buffer solutions of pH 1.2, 4.6, and 7.4, respectively. Maximum swelling and drug release were observed at higher pH values as compared to the lower pH value due to the deprotonation and protonation of functional groups of the hydrogel contents; thus, the pH-sensitive nature of the fabricated hydrogel was demonstrated. Likewise, water penetration capability and polymer volume were evaluated by porosity and polymer volume studies. Increased incorporation of β-cyclodextrin, acrylic acid, and itaconic acid led to an increase in swelling, drug release, drug loading, and porosity of the fabricated hydrogel, whereas a decrease was detected with the increasing concentration of ethylene glycol dimethacrylate. Conclusively, the prepared hydrogel could be employed as a suitable and promising carrier for the controlled release of theophylline.

The development and optimisation of gastro-retentive floating tablets using fused deposition modelling 3D printing.

To develop a robust tablet design for the manufacture of gastro-retentive tablets using fused deposition modelling three-dimensional printing (FDM-3DP) that can provide prolonged gastric residence time with instant floating and minimum influence of process and/or formulation variables. Three different polymers, such as polyvinyl alcohol (PVA), hydroxypropyl cellulose (HPC) and Soluplus were used, separately, for the manufacture of tablets using FDM-3DP. Tablets were designed in a sandwich model that included voids in the internal structure to support buoyancy. Fabricated tablets from all polymers were instantly buoyant with no floating lag time. Floating duration was in the order: HPC > Soluplus > PVA which can be explained by the density of the tablets. PVA tablets exhibited significantly (P < 0.05) higher density values (0.86±0.02mg/mm3) than HPC and Soluplus (0.69±0.03 and 0.72±0.02mg/mm3, respectively). HPC and Soluplus showed similar zero-order drug release profiles (f2 > 50) and were able to sustain the release of theophylline for 12h, whereas complete drug release was achieved from PVA tablets after 3h. Robust gastro-retentive tablets that show instant buoyancy regardless of the polymeric carrier type and composition were successfully manufactured utilising FDM-3DP. This allows for overcoming the restrictions posed by process/formulation parameters on the floatability of gastro-retentive tablets.

Salification Controls the In-Vitro Release of Theophylline

Sustained released formulation is the most used strategy to control the efficacy and the adverse reactions of an API (active pharmaceutical ingredient) with a narrow therapeutic index. In this work, we used a different way to tailor the solubility and diffusion of a drug. Salification of Theophylline with Squaric Acid was carried out to better control the absorption of Theophylline after administration. Salification proved to be a winning strategy decreasing the dissolution of the APIs up to 54% with respect to Theophylline. Most importantly, this was accomplished in the first 10 min of the dissolution process, which are the most important for the API administration. Two polymorphs were identified and fully characterized. Theophylline squarate was discovered as trihydrate (SC-XRD) and as a metastable anhydrous form. Indeed, during the Variable Temperature-XRPD experiment, the trihydrate form turned back into the two starting components after losing the three molecules of water. On the other hand, the synthesis of the trihydrate form was observed when a simple mixing of the two starting components were exposed to a high humidity relative percentage (90% RH).

In vivo Evaluation of Theophylline Sustained Release Matrix Tablets Containing Low Viscosity Guar Gum

The present investigation was carried out to evaluate the utility of guar gum as a hydrophilic matrix carrier in the design of oral controlled drug delivery. Based on the earlier reports, the low viscosity guar gum appears to be superior to medium and high viscosity grades of guar gum in providing a sustained delivery of theophylline along the GI tract. Conducting in vivo studies on theophylline matrix tablets containing 10% of low viscosity guar gum as a representative formulation assessed the in vivo performance of the guar gum matrix tablets. The in vivo studies were carried out in dogs. The effective concentration of theophylline was sustained for a period of 16 hours. The extended tmax, reduced absorption rate constant, prolonged MRT, unchanged Cmax and unchanged bioavailability indicate a controlled release of theophylline from the guar gum matrix tablets resulting in a sustained absorption and prolonged blood levels of theophylline. The theophylline matrix tablets showed blood levels well below 15 ?g/mL indicating freedom from adverse effects. Based on the studies, guar gum appears to be a potential carrier in the design of oral controlled drug delivery systems.

Fabrication of alginate based microgels for drug-sustained release: In-vitro and in-vivo evaluation

The current study was conducted to evaluate and analyze the effect of alginate, itaconic acid, and N,N′-methylene bisacrylamide in formulation of a novel alginate based microgels for sustained release of theophylline. The fabricated microgels were characterized by PXRD, SEM, FTIR, TGA and DSC respectively. FTIR revealed that alginate reacted with itaconic acid during polymerization reaction and confirmed the overlapping of itaconic acid on the backbone of alginate. TGA and DSC depicted high thermal stability of the fabricated microgels as compared to pure unreacted polymer and monomer. Likewise, dynamic swelling and percent drug release studies were carried out at different pH media i.e., pH 1.2, 4.6 and 7.4 respectively. Greater dynamic swelling and percent drug release was observed at higher pH 7.4 as compared to lower pH 4.6 and 1.2 due to the deprotonation of COOH groups of both alginate and itaconic acid respectively. The drug release mechanism from the fabricated microgels could be described by first order model. In-vivo pharmacokinetic study was performed on rabbits and exhibited sustained release in rabbits. Hence, the developed microgels indicated higher potential as the delivery system for the sustained delivery of theophylline.