Low-viscosity hydroxypropyl methylcellulose obtained by electron beam irradiation and its performance in spray drying.

Low-viscosity hydroxypropyl methylcellulose (HPMC) was obtained by electron beam irradiation, and its use as an excipient for improving the properties of spray dried pharmaceutical powders was investigated. The minimum molecular weight of HPMC which could maintain the capacity of encapsulation and powder modification was explored. As the irradiation dose was increased from 10 to 200 kGy, the molecular weight and viscosity of HPMC decreased linearly. However, its main structure and degrees of methoxy and hydroxypropyl substitution were not significantly affected. The irradiated HPMC could encapsulate particles during spray drying and, thus, modify powder properties. Furthermore, the water content of spray-dried powders with irradiated HPMC was lower than that with parent HPMC. After the spray-dried powder with irradiated HPMC was prepared into granules, their dissolution rate was also faster. However, in order to achieve high encapsulation, the molecular weight of HPMC should be ensured to be above 7.5 kDa. The designated low-viscosity HPMC obtained by electron beam irradiation is a suitable powder-modification material for use in spray drying, and it shows promise as a superior excipient in medicine, food, paint industries, among others.

Highly sensitive two-dimensional ion chromatography mass spectrometry method for nitrite determination in hydroxypropyl methylcellulose.

Due to their potential adverse health effects, some N-nitrosamines in drug products are strictly regulated with very low maximum daily intake limits. Nitrosamines can be formed from the reaction of nitrite and secondary or tertiary amines when both species co-exist in the drug synthesis or formulation process. One key strategy to mitigate nitrosamine risk in drugs is to select low-nitrite containing pharma excipients for formulation. It is necessary to develop a sensitive method for trace nitrite determination in pharma excipients as it enables drug producers to study nitrosamine formation kinetics and select excipient suppliers. This study details the development and validation of a two-dimensional ion chromatography mass spectrometry (2D-IC/MS) method for trace nitrite determination in hydroxypropyl methylcellulose (HPMC), one of the most important pharmaceutical excipients used in many drug formulations. The 2D-IC system was operated in heart-cutting mode with a concentrator column coupling the two dimensions. A standard bore anion-exchange column was used in the first dimension (1D) to enable a large volume injection for increased sensitivity and provide improved resolution between nitrite and the interfering chloride peak. A high efficiency microbore anion-exchange column with different selectivity was used in the second dimension (2D) to resolve nitrite from other interfering species. The use of 2D-IC resulted in significantly improved resolution, solving the sensitivity loss issue due to ion suppression from an otherwise 1D separation. MS detection with selective ion monitoring and isotope labeled nitrite internal standard further improve the method specificity, accuracy, and ruggedness, as compared with conductivity detection. For trace determination, it is also extremely important to have a clean blank. For this purpose, a novel cleaning procedure using a strong anion wash was developed to remove nitrite contamination from labware. The optimized method was validated with linearity of nitrite in the concentration range of 18.5-5005.8 ng/g having a regression coefficient of >0.9999, precision with RSD at 3.5-10.1 % and recovery of 90.5-102.4 %. The limit of detection and limit of quantitation were 8.9 and 29.6 ng/g relative to the HPMC sample, or equivalent to 89 and 296 pg/g in the sample solution, respectively.

Diltiazem Hydrochloride Floating Matrix Tablet: Formulation and in vitro-in vivo Evaluation.

BACKGROUND: Diltiazem hydrochloride is a calcium channel-blocker with a plasma elimination half-life of 4.4 ± 1.3 h and has a narrow absorption window. So, this work aimed to prepare a gastro-retentive floating matrix tablet. METHODS: The direct compression method was used to manufacture tablets. 32 factorial design was applied for optimization, taking Hydroxypropyl Methylcellulose K100M (HPMC K 100M) and the amount of sodium bicarbonate as independent factors and cumulative percentage release at 1 h, at 6 h, and at 12 h and floating lag time as dependent variables. RESULTS: The high amount of HPMC K100M and sodium bicarbonate shows good results. The optimized preparation was evaluated for differential scanning calorimetry, in-vivo gastric retention in male albino rabbits, kinetic modeling, and stability study. An in vivo study revealed gastric retention of tablets up to 6 h in healthy male Albino rabbits. The stability study indicated no significant change in the buoyancy and release profiles of the drug. CONCLUSION: From this study, it can be concluded that the gastro-retentive diltiazem hydrochloride floating matrix tablet was successfully prepared and retained inside the rabbit stomach for up to 6 h and was stable under accelerated stability study.

The application of film based on gelatin/hydroxymethyl cellulose and red beetroot betalain in smart food packaging.

Edible films containing anthocyanin and betacyanin as indicators of freshness are promising systems for food smart packaging. This research aimed to develop a smart color film for food packaging using gelatin/hydroxypropylmethyl cellulose (HPMC) and red beet betalain. In this study, edible films with different ratios of gelatin to HPMC were prepared successfully, and the ratio of 3:1 was determined as optimal samples based on water vapor permeability (WVP) and mechanical properties. Betalain with different concentrations was then added to the optimal film, and the physical and mechanical properties of the resulting films were evaluated. Also, TVB-N test to assess their ability to detect beef meat and shrimp spoilage was studied. The addition of betalain improved the solubility, WVP, mechanical properties, and 2,2-diphenyl-l-picrylhydrazyl free radical scavenging activity of the film. As a final point, the incorporation of betalain into the gelatin/HPMC films can be used to indicate the freshness of food.

Enhancing Gluten-Free Bread Production: Impact of Hydroxypropyl Methylcellulose, Psyllium Husk Fiber, and Xanthan Gum on Dough Characteristics and Bread Quality.

The demand for gluten-free products has increased due to improved diagnoses and awareness of gluten-related issues. This study investigated the effect of HPMC, psyllium, and xanthan gum in gluten-free bread formulations. Three tests were conducted, varying the amount of these ingredients: in the first formulation, the amount of HPMC was increased to 4.4 g/100 g of flour and starch; in the second, psyllium husk fiber was increased to 13.2 g/100 g of flour and starch; and in the third formulation, xanthan gum was removed. Differences were observed among the formulations: increasing HPMC reduced extrusion force without affecting bread quality; adding psyllium increased dough elasticity but also crumb gumminess and crust hardness. Eliminating xanthan gum altered dough rheology, resulting in a softer and less gummy crumb, and a less reddish color in the final bread.

Effect of Cremophor RH40, Hydroxypropyl Methylcellulose, and Mixing Speed on Physicochemical Properties of Films Containing Nanostructured Lipid Carriers Loaded with Furosemide Using the Box-Behnken Design.

This study aimed to examine the characteristics of H-K4M hydroxypropyl methylcellulose (HPMC) films containing nanostructured lipid carriers (NLCs) loaded with furosemide. A hot homogenization technique and an ultrasonic probe were used to prepare and reduce the size of the NLCs. Films were made using the casting technique. This study used a Box-Behnken design to evaluate the influence of three key independent variables, specifically H-K4M concentration (X1), surfactant Cremophor RH40 concentration (X2), and mixing speed (X3), on the physicochemical properties of furosemide-loaded NLCs and films. The furosemide-loaded NLCs had a particle size ranging from 54.67 to 99.13 nm, and a polydispersity index (PDI) ranging from 0.246 to 0.670. All formulations exhibited a negative zeta potential, ranging from -7.05 to -5.61 mV. The prepared films had thicknesses and weights ranging from 0.1240 to 0.2034 mm and 0.0283 to 0.0450 g, respectively. The drug content was over 85%. Film surface wettability was assessed based on the contact angle, ranging from 32.27 to 68.94°. Film tensile strength varied from 1.38 to 7.77 MPa, and their elongation at break varied from 124.19 to 170.72%. The ATR-FTIR analysis confirmed the complete incorporation of the drug in the film matrix. Therefore, the appropriate selection of values for key parameters in the synthesis of HPMC films containing drug-loaded NLCs is important in the effective development of films for medical applications.

Preparation and Properties of Polyaniline/Hydroxypropyl Methylcellulose Composite Conductive Thin Films.

In this work, a chemical grafting polymerization method was employed to synthesize EHPMC-g-PANI self-supporting films. Polyaniline (PANI) was grafted onto hydroxypropyl methylcellulose (HPMC) modified with epichlorohydrin (EPHMC) to obtain an EHPMC-g-PANI aqueous dispersion, which was subsequently dried to form the self-supporting films. The introduction of HPMC, with its excellent film-forming ability and mechanical strength, successfully addressed the poor film-forming ability and mechanical properties intrinsic to PANI. Compared to in situ polymerized HPMC/PANI, the EHPMC-g-PANI exhibited significantly improved storage stability. Moreover, the fabricated EHPMC-g-PANI films displayed a more uniform and smoother morphology. The conductivity of all the films ranged from 10-2 to 10-1 S/cm, and their tensile strength reached up to 36.1 MPa. These results demonstrate that the prepared EHPMC-g-PANI holds promising potential for applications in various fields, including conductive paper, sensors, and conductive inks.

The Effects of Hydroxypropyl Methyl Cellulose and Metakaolin on the Properties of Self-Compacting Solidified Soil Based on Abandoned Slurry.

As a new type of backfill material, Self-compacting solidified soil (SCSS) takes the abandoned slurry of cast-in-place piles after dewatering and reduction as the main raw material, which brings a problem of coordinating the working performance with the mechanical property under the condition of high mobility. In this paper, hydroxypropyl methyl cellulose (HPMC) and metakaolin were introduced as additives to solve this problem. First, the workability and mechanical properties of SCSS were regulated and optimized by means of the water seepage rate test, the flowability test, and the unconfined compressive strength test. Second, this study also used X-ray diffraction (XRD) and scanning electron microscopy (SEM) to investigate the effects of HPMC and metakaolin on the physical phase and microstructure of SCSS. In this way, the results showed that there was a significant impact on the flowability of SCSS, that is, when the dosage reached 0.3%, the water seepage rate of SCSS was reduced to less than 1%, and the compressive strength at 7 days reached its peak. At the same time, HPMC weakened the strength growth of SCSS in the age period of 7 days to 14 days. However, the addition of metakaolin promoted its compressive strength. XRD analysis showed that the additives had no significant effects on the physical phases. And, from the SEM results, it can be seen that although the water-retaining effect of HPMC makes hydration of cement more exhaustive, more ettringite (AFt) can be observed in the microstructure. In addition, it can be observed that the addition of metakaolin can generate more hydrated calcium silicate (C-S-H) due to the strong surface energy possessed by metakaolin. As a result of the above factors, SCSS filled the voids between particles and improved the interface structure between particles, thus enhanced the compressive strength.

Formulation and Evaluation of Polysaccharide Microparticles for the Controlled Release of Propranolol Hydrochloride.

Propranolol hydrochloride, a non-cardio-selective beta blocker, is used to treat several conditions in children, including hypertension, arrhythmias, hyperthyroidism, hemangiomas, etc. Commercial liquid formulations are available in Europe and the US, but they have disadvantages, such as limited stability, bitter taste, and the need for multiple daily doses due to the drug's short half-life. Considering these limitations, controlled-release solid formulations, such as microparticles, may offer a better solution for pediatric administration. The main objective of this study was to formulate an encapsulation system for propranolol hydrochloride, based on sodium alginate and other polysaccharide polymers, to control and prolong its release. Microparticles were prepared using the ionotropic gelation method, which involves instilling a polymer solution into a solution of gelling ions via the extrusion technique. Physicochemical characterization was conducted by assessing the entrapment efficiency, drug loading, swelling index, microparticle size, rheological properties, and surface tension. In order to improve the characteristics of the tested microparticles, selected formulations were coated with chitosan. Further experimental work included differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) analysis, and SEM imaging. This in vitro release study showed that chitosan-coated microparticles demonstrate favorable properties, suggesting a novel approach to formulating pediatric dosage forms, although further optimization is necessary.

Development of active film based on collagen and hydroxypropyl methylcellulose incorporating apple polyphenol for food packaging.

Collagen (COL)-hydroxypropyl methylcellulose (HPMC) blended films with apple polyphenol (AP) as cross-linking agent and antioxidant compound were developed to produce biodegradable active packaging film. The effects of AP content on the rheological behavior of the blended solution, the structure, physicochemical and functional properties of the blended film were systematically investigated. The incorporation of AP increased the viscosity and reduced the fluidity of COL-HPMC solution. The results of rheological tests and FTIR analysis manifested the formation of hydrogen bonding interactions between collagen, HPMC and AP, which made the structures of COL-HP-AP films more compact. The mechanical strength, UV-blocking ability, water-resistance performance and thermostability were gradually enhanced as increasing AP content. DPPH free radical scavenging experiment showed that a small amount of AP could efficiently improve the antioxidant activity of COL-HP film, and with increasing AP content to 5 wt%, the scavenging rate was as high as 94.23 %. Active film containing 5 wt% AP showed obvious antibacterial effect on E. coli and S. aureus, and it could effectively prevent the oxidation of vitamin C and reduce the accumulation of MDA on green pepper during the storage. COL-HP-AP films have great potential in food packaging field for extending the shelf life of food.

Mannitol-coated hydroxypropyl methylcellulose as an alternative directly compressible controlled release excipient.

One of the most common forms of controlled release technology for oral drug delivery comprises an active ingredient dispersed in a hydrophilic matrix forming polymer such as hydroxypropyl methylcellulose (HPMC), which is tableted via direct compression. However, HPMC may pose problems in direct compression due to its poor flowability. Hence, mannitol syrup was spray-coated over fluidized HPMC particles to produce co-processed HPMC-mannitol at ratios of 20:80, 50:50, and 70:30. Particles of pure HPMC, co-processed HPMC-mannitol, and their respective physical mixtures were evaluated for powder flowability, compression profiles, and controlled release performance. It was found that co-processed HPMC-mannitol consisted of particles with improved flow compared to pure HPMC particles. Sufficiently strong tablets of >2 MPa could be produced at moderate to high compression forces of 150-200 MPa. The dissolution profile could be tuned to obtain desired release profiles by altering HPMC-mannitol ratios. Co-processed HPMC-mannitol offers an interesting addition to the formulator's toolbox in the design of controlled release formulations for direct compression.

Multiscale structure analysis of a pH-responsive gelatin/hydroxypropyl methylcellulose phthalate blend using small-angle scattering.

HYPOTHESIS: Hydroxypropyl methylcellulose phthalate (HPMCP) is an enteric polymer that has been employed in drug delivery systems to delay the release of the encapsulated active pharmaceutical ingredients through its pH-responsive solubility change. This has been recently demonstrated as an effective means for delaying the drug release from gelatin/HPMCP hydrogels at gastric pH values. However, structural characteristics of HPMCP agglomeration in gelatin/HPMCP hydrogels is not well understood thus limiting further tailoring of their material properties. EXPERIMENTS: We investigated the multiscale structure of a gelatin/HPMCP hydrogel (1:1 by weight) between pH 2 and 6 at 37 °C, i.e. above the upper critical solution transition temperature of gelatin, using small-angle X-ray scattering and contrast-variation small-angle neutron scattering to understand the pH-responsive structure of HPMCP and the cross-correlation between gelatin and HPMCP. FINDINGS: Agglomeration of HPMCP between pH 2 and 4 was evidenced by the formation of mass fractal structures, with a fractal dimension ranging from 1.5 to 2.7, comprising primary particles with a radius of gyration ranging from 70 to 140 Å. Blending with gelatin influenced the fractal structure of HPMCP and the primary particle size. Gelatin and HPMCP exhibited negative cross-correlation in all probed length scales and pH values, which was attributed to volume-exclusion interaction in a double-network-like solution architecture.

Effect of Different Hydrocolloids on the Qualitative Characteristics of Fermented Gluten-Free Quinoa Dough and Bread.

The aim of this research was to optimize the production process of fermented gluten-free quinoa bread. To this end, the effect of different hydrocolloids on the technological, fermentative, and nutritional properties of quinoa-based gluten-free doughs and breads was evaluated. For this purpose, 3% of four different hydrocolloids (sodium alginate, k-carrageenan, xanthan gum, and hydroxypropyl methylcellulose (HPMC)) were used in gluten-free doughs composed of 50% quinoa flour, 20% rice flour, and 30% potato starch. The rheological and fermentative properties of the doughs were evaluated, as well as the chemical composition, specific volume, crust and crumb color, and alveolar structure profile of gluten-free breads. The results highlighted the differences in dough rheology during mixing and fermentation of the doughs. In particular, HPMC showed a good gas retention (93%) during the fermentation of quinoa dough by registering the highest maximum dough development height (Hm). The gluten-free quinoa breads obtained were characterized by significantly different quality parameters (p < 0.05). The use of 3% HPMC resulted in breads with the lowest baking loss, the highest volume, and the most open crumb structure.

Improvement of anti-prion efficacy with stearoxy conjugation of hydroxypropyl methylcellulose in prion-infected mice.

Prion diseases are fatal transmissible neurodegenerative disorders. Among known anti-prions, hydroxypropyl methylcellulose compounds (HPMCs) are unique in their chemical structure and action. They have several excellent anti-prion properties but the effectiveness depends on the prion-infected mouse model. In the present study, we investigated the effects of stearoxy-modified HPMCs on prion-infected cells and mice. Stearoxy modification improved the anti-prion efficacy of HPMCs in prion-infected cells and significantly prolonged the incubation period in a lower HPMC-responding mouse model. However, stearoxy modification showed no improvement over nonmodified HPMCs in an HPMC-responding mouse model. These results offer a new line of inquiry for use with prion-infected mice that do not respond well to HPMCs.

Integrated Janus nanofibers enabled by a co-shell solvent for enhancing icariin delivery efficiency.

During the past several decades, nanostructures have played their increasing influences on the developments of novel nano drug delivery systems, among which, double-chamber Janus nanostructure is a popular one. In this study, a new tri-channel spinneret was developed, in which two parallel metal capillaries were nested into another metal capillary in a core-shell manner. A tri-fluid electrospinning was conducted with a solvent mixture as the shell working fluid for ensuring the formation of an integrated Janus nanostructure. The scanning electronic microscopic results demonstrated that the resultant nanofibers had a linear morphology and two distinct compartments within them, as indicated by the image of a cross-section. Fourier Transformation Infra-Red spectra and X-Ray Diffraction patterns verified that the loaded poorly water-soluble drug, i.e. icariin, presented in the Janus medicated nanofibers in an amorphous state, which should be attributed to the favorable secondary interactions between icariin and the two soluble polymeric matrices, i.e. hydroxypropyl methyl cellulose (HPMC) and polyvinylpyrrolidone (PVP). The in vitro dissolution tests revealed that icariin, when encapsulated within the Janus nanofibers, exhibited complete release within a duration of 5 min, which was over 11 times faster compared to the raw drug particles. Furthermore, the ex vivo permeation tests demonstrated that the permeation rate of icariin was 16.2 times higher than that of the drug powders. This improvement was attributed to both the rapid dissolution of the drug and the pre-release of the trans-membrane enhancer sodium lauryl sulfate from the PVP side of the nanofibers. Mechanisms for microformation, drug release, and permeation were proposed. Based on the methodologies outlined in this study, numerous novel Janus nanostructure-based nano drug delivery systems can be developed for poorly water-soluble drugs in the future.

Hydrolysis of Cellulose Acetate Phthalate and Hydroxypropyl Methylcellulose Phthalate in Amorphous Solid Dispersions.

The preparation of amorphous solid dispersions (ASDs) represents a promising strategy for addressing the solubility limitations of poorly soluble drugs, facilitating enhanced oral absorption. Acidic polymers such as cellulose acetate phthalate (CAP) and hydroxypropyl methylcellulose phthalate (HPMCP) have emerged as effective carriers for ASDs. Although the hydrolytic degradation of these polymers has been documented, its impact on the stability of ASDs has not been systematically investigated. This research aimed to explore the potential hydrolysis of CAP and HPMCP and how it influences the stability of ASDs containing ketoconazole (KTZ), at drug loadings of 10 % and 50 %. Our study utilized thermal analysis, infrared spectroscopy, and evaluations of physical and chemical stability. The results revealed that although KTZ remained physically stable in all ASDs over 60 days under various stability conditions, the emergence of crystalline phthalic acid (PA), a byproduct of polymer hydrolysis, was observed at elevated temperatures and relative humidity levels. The acidic microenvironment fostered by the release of PA further catalyzed drug chemical degradation. This study underscores the susceptibility of CAP and HPMCP to hydrolytic degradation, highlighting the inherent risk of PA-induced drug degradation, particularly for acid-labile compounds. These insights into the understanding of polymer hydrolysis in ASDs pave the way for the development of targeted approaches to safeguard drug stability and optimize pharmaceutical formulations for enhanced bioavailability, efficacy, and safety.

Effect of zein-pectin composite particles on the stability and rheological properties of gelatin/hydroxypropyl methylcellulose water-water systems.

To improve the compatibility of gelatin (GA) and hydroxypropyl methylcellulose (HPMC), we investigated the effects of zein-pectin composite particles (ZCPs) with various zein/pectin ratios (1:0, 1:0.5, 1:1, 1:1.5, and 1:2) on the physical stability, microstructure, and rheological properties of the GA/HPMC water-water systems. With increasing pectin ratio, the particle size of the composite particles increased from 234.53 ± 1.48 nm to 1111.00 ± 26.91 nm, and their zeta potential decreased from 20.60 mV to below -34.77 mV. Macroscopic and microstructure observations indicated that pectin-modified ZCPs could effectively inhibit phase separation behavior between GA and HPMC. Compared to pure HPMC, the GA/HPMC water-water systems possessed a higher viscosity and dynamic modulus at room temperatures but lower gel temperatures (reduction of about 11 %). The viscosity and modulus of the water-water systems increased with increasing pectin ratio in ZCPs. However, the ratio had no impact on the gel-sol (sol-gel) transition temperatures (not statistically significant (P < 0.05)). This study may serve as a reference for advancing the processability of HPMC.

Development of a hydroxypropyl methyl cellulose/polyacrylic acid interpolymer complex formulated buccal mucosa adhesive film to facilitate the delivery of insulin for diabetes treatment.

Buccal mucosa administration is a promising method for insulin (INS) delivery with good compliance. However, buccal mucosa delivery systems still face challenges of long-term mucosal adhesion, sustained drug release, and mucosal drug penetration. To address these issues, a double-layer film consisting of a hydroxypropyl methylcellulose/polyacrylic acid interpolymer complex (IPC)-formulated mucoadhesive layer and an ethylcellulose (EC)-formulated waterproof backing layer (IPC/EC film) was designed. Protamine (PTM) and INS were co-loaded in the mucoadhesive layer of the IPC/EC film (PTM-INS-IPC/EC film). In ex vivo studies with porcine buccal mucosa, this film exhibited robust adhesion, with an adhesion force of 120.2 ±â€¯20.3 N/m2 and an adhesion duration of 491 ±â€¯45 min. PTM has been shown to facilitate INS mucosal transfer. Pharmacokinetic studies indicated that the PTM-INS-IPC/EC film significantly improved the absorption of INS, exhibiting a 1.45 and 2.24-fold increase in the area under the concentration-time curve (AUC0-∞) compared to the INS-IPC/EC film and free INS, respectively. Moreover, the PTM-INS-IPC/EC film effectively stabilized the blood glucose levels of type 1 diabetes mellitus (T1DM) rats with post oral glucose administration, maintaining lower glucose levels for approximately 8 h. Hence, the PTM-INS-IPC/EC film provides a promising noninvasive INS delivery system for diabetes treatment.

Studying the API Distribution of Controlled Release Formulations Produced via Continuous Twin-Screw Wet Granulation: Influence of Matrix Former, Filler and Process Parameters.

Hydroxypropyl methylcellulose (HPMC) is a preferred hydrophilic matrix former for controlled release formulations produced through continuous twin-screw wet granulation. However, a non-homogeneous API distribution over sieve fractions with underdosing in the fines fraction (<150 µm) was previously reported. This could result in content uniformity issues during downstream processing. Therefore, the current study investigated the root cause of the non-homogeneous theophylline distribution. The effect of process parameters (L/S-ratio and screw configuration) and formulation parameters (matrix former and filler type) on content uniformity was studied. Next, the influence of the formulation parameters on tableting and dissolution behavior was investigated. Altering the L/S-ratio or using a more aggressive screw configuration did not result in a homogeneous API distribution over the granule sieve fractions. Using microcrystalline cellulose (MCC) as filler improved the API distribution due to its similar behavior as HPMC. As excluding HPMC or including a hydrophobic matrix former (Kollidon SR) yielded granules with a homogeneous API distribution, HPMC was identified as the root cause of the non-homogeneous API distribution. This was linked to its fast hydration and swelling (irrespective of the HPMC grade) upon addition of the granulation liquid.

Preparation and Characterization of Theophylline Controlled Release Matrix System Incorporating Poloxamer 407, Stearyl Alcohol, and Hydroxypropyl Methylcellulose: A Novel Formulation and Development Study.

BACKGROUND: Theophylline (THN), a bronchodilator with potential applications in emerging conditions like COVID-19, requires a controlled-release delivery system due to its narrow therapeutic range and short half-life. This need is particularly crucial as some existing formulations demonstrate impaired functionality. This study aims to develop a new 12-h controlled-release matrix system (CRMS) in the form of a capsule to optimize dosing intervals. METHODS: CRMSs were developed using varying proportions of poloxamer 407 (P-407), stearyl alcohol (STA), and hydroxypropyl methylcellulose (HPMC) through the fusion technique. Their in vitro dissolution profiles were then compared with an FDA-approved THN drug across different pH media. The candidate formulation underwent characterization using X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and thermogravimetric analysis. Additionally, a comprehensive stability study was conducted. RESULTS: In vitro studies showed that adjusting the concentrations of excipients effectively controlled drug release. Notably, the CRMS formulation 15 (CRMS-F15), which was composed of 30% P-407, 30% STA, and 10% HPMC, closely matched the 12 h controlled-release profile of an FDA-approved drug across various pH media. Characterization techniques verified the successful dispersion of the drug within the matrix. Furthermore, CRMS-F15 maintained a consistent controlled drug release and demonstrated stability under a range of storage conditions. CONCLUSIONS: The newly developed CRMS-F15 achieved a 12 h controlled release, comparable to its FDA-approved counterpart.