Co-processed Excipient Research Articles

A Development of a Novel Co-processed Excipient Comprising of Microcrystalline Cellulose, Xylitol, Mannitol, and Crospovidone for Orally Disintegrating Tablets

A Development of a Novel Co-processed Excipient Comprising of Microcrystalline Cellulose, Xylitol, Mannitol, and Crospovidone for Orally Disintegrating Tablets

Development of Chitosan-Maize Starch based Co-processed excipient: As release retardant material

In the present study, co-processed excipients from chitosan, and maize starch were prepared by co-dispersion, and co-granulation methods in 1:1 ratio. The resultant products were then characterized physically by their micrometric properties and hygroscopic characters. The co-processed excipient prepared by co-granulation was chosen and was added to a directly compressible oral sustained-release tablet (Batch F1-F4) containing ibuprofen as a model drug. A well-known marketed ibuprofen tablet (Motrin) was taken for comparison purposes of the dissolution characteristics. Pre-compression parameters, as well as post-compression parameters of all the batches, were performed. The pre-compression parameters, and post-compression parameters of F3, containing chitosan to maize in the ratio of 2:1, were found to be comparable with the marketed product. F3 batch showed 74.7 % of drug release up to 8 h, which reflect the release retardant properties of co-processed excipient. Collectively, co-processed excipients of chitosan, and maize starch improve the physical properties of individual materials, and can be used as a directly compressible excipient as a release retardant material for oral sustained-release tablets.

Understanding Powder Behavior in Continuous Feeding: Powder Densification and Screw Layering

Background: Precise continuous feeding of active pharmaceutical ingredients (APIs) and excipients is crucial in a continuous powder-to-tablet manufacturing setup, as any inconsistency can affect the final tablet quality. Method: This study investigated the impact of various materials on the performance of a continuous twin-screw loss-in-weight (LIW) feeder. The materials tested included spray-dried lactose, anhydrous lactose, granulated lactose, microcrystalline cellulose (MCC), an MCC–lactose preblend (50%:50% w/w ratio), and a co-processed excipient (lactose–lactitol at a 95%:5% w/w ratio). The feeding performance of these excipients was systematically assessed, focusing on powder densification and screw layering within the LIW feeder. Results: The results demonstrated densification for the spray-dried lactose and preblend. Densification was more pronounced during the initial feeding cycles for spray-dried lactose, but decreased gradually over time. In contrast, the densification remained relatively constant throughout the feeding process for the preblend. Notably, minor screw layering was observed for both spray-dried lactose and anhydrous lactose, with the extent of this issue reducing over time for the spray-dried lactose. Interestingly, granulated lactose grades did not show screw layering, making them preferable for blending with APIs prone to severe screw layering. The LIW feeder control system successfully managed powder densification and minor screw layering, maintaining the mass flow rate at the set point for all investigated materials. Conclusions: These findings inform the selection of optimal excipients, appropriate tooling for LIW feeders, and the enhancement of control strategies to shorten startup times. By addressing these factors, the precision and reliability of continuous feeding processes can be improved.

"Preparation And Characterization Of Co-Processed Excipient For Enhancement Of Physicochemical Properties"

"Preparation And Characterization Of Co-Processed Excipient For Enhancement Of Physicochemical Properties"

Development of Orodispersible Tablets with Solid Dispersions of Fenofibrate and Co-Processed Mesoporous Silica for Improved Dissolution.

Poor water solubility is an important challenge in the development of oral patient-friendly solid dosage forms. This study aimed to prepare orodispersible tablets with solid dispersions of a poorly water-soluble drug fenofibrate and a co-processed excipient consisting of mesoporous silica and isomalt. This co-processed excipient, developed in a previous study, exhibited improved flow and compression properties compared to pure silica while maintaining a high specific surface area for drug adsorption. Rotary evaporation was used to formulate solid dispersions with different amounts of fenofibrate, which were evaluated for solid state properties and drug release. The solid dispersion with 30% fenofibrate showed no signs of crystallinity and had a significantly improved dissolution rate, making it the optimal sample for formulation or orodispersible tablets. The aim was to produce tablets with minimal amounts of additional excipients while achieving a drug release profile similar to the uncompressed solid dispersion. The compressed formulations met the requirements for orodispersible tablets in terms of disintegration time, and the drug release from best formulation approximated the profile of uncompressed solid dispersion. Future research should focus on reducing the disintegration time and tablet size to enhance patient acceptability further.

A Novel Lactose/MCC/L-HPC Triple-Based Co-Processed Excipients with Improved Tableting Performance Designed for Metoclopramide Orally Disintegrating Tablets.

New co-processed excipients comprising lactose (filler and sweetener), microcrystalline cellulose (MCC, filler), and low-substituted hydroxypropyl cellulose (L-HPC, disintegrant and binder) were developed via solvent evaporation for the preparation of metoclopramide orally disintegrating tablets (MCP ODTs). Single-factor and Box-Behnken experimental designs were employed to optimize the formulation. The optimized formulation ratios were water: MCC: lactose (g/g) = 17.26:2.79:4.54:1. The results demonstrated that particles formed by solvent evaporation had superior flowability and compressibility compared to the physical mixture. Tablets compressed with these co-processed excipients exhibited a significantly reduced disintegration time of less than 25 s and achieved complete dissolution within 5 min. Pharmacokinetic studies revealed that MCP ODTs significantly improved Cmax, which was 1.60-fold higher compared to conventional tablets. In summary, the lactose/L-HPC/MCC triple-based co-processed excipients developed in this study are promising and could be successfully utilized in orally disintegrating and fast-release tablets.

The Effect of PEG 4000 in Co-processed Excipient using Melt Granulation Method on the Physical Characteristics of Chitosan Tablets in Mangrove Crab Shells (Scylla serrata)

The Effect of PEG 4000 in Co-processed Excipient using Melt Granulation Method on the Physical Characteristics of Chitosan Tablets in Mangrove Crab Shells (Scylla serrata)

Design and Development of Fast-dissolving Tablets of Apixaban using Single Coprocessed Excipient

Background: Apixaban is administered orally as an anticoagulant action and minimizes the chances of strokes and systemic embolism. The conventional film-coated tablet showed less bioavailability due to its minimal solubility in the gastrointestinal tract. Rationale: The goal of designing the current analysis is to prepare a prompt release tablet using a single Coprocessed excipient which minimizes multistep processing, time, and cost effectiveness. Methods: The prompt release tablets of Apixaban were developed by direct compression technique using multifunctional material like Prosolve ODT G2 and Prosolve Easytab. Drug excipients inertness was confirmed with FTIR and DSC. Flowing characteristics of Apixaban and co-processed excipients were evaluated in terms of Carr’s index, Angle of repose, and Hausner’s ratio. These co-processed excipients indicated exceptional flowing and compression characteristics. The ready tablets were assessed for weight variation, hardness, friability, dispersion time, disintegration, and dissolution studies. Results: Among 12 batches, the least disintegration time was shown with C6 with a cumulative drug release of 99.06 % within 25 min. The optimized batch C6 was highly stable when tested under stability guidelines at 40 0 C and at 75 % relative humidity. Conclusion: Among these co-processed excipients, Prosolve Easytab SP was found the best one for direct compression intended for the immediate or fast dissolving tablets.

CELLULOSE NANOCRYSTAL-INCORPORATED CO-PROCESSED EXCIPIENT IN TABLET FORMULATION

The objective of the current work is to develop a new co-processed excipient based on cellulose nanocrystals and investigate its pharmaceutical excipient properties. Cellulose nanocrystals were isolated from the pseudostem of Musa balbisiana, following TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy)-mediated oxidation, and then co-processed with potato starch by the wet granulation method. Physicochemical properties, including the flow property, consolidation characteristics and rate of consolidation, were investigated, and a Kawakita plot was also generated. The compressibility, compactibility and tabletability of the novel excipient were determined. The equivalent circle diameter of the excipient particle was calculated as 4.09±0.90 μm, exhibiting a fair to passable flow property. The mean yield pressure from the Heckel plot was found to be 82.64 MPa, indicating its ability to undergo plastic deformation at relatively lower compression pressures. When compared to sodium starch glycolate, a standard tablet disintegrant, the cellulose nanocrystal-based co-processed excipient produced better dissolution of the model drug paracetamol.

The Effect of PEG 4000 in Co-processed Excipient using Melt Granulation Method on the Physical Characteristics of Chitosan Tablets in Mangrove Crab Shells (Scylla serrata)

Mangrove Crab (Scylla serrata) is an animal that likes to be consumed but its shell waste is underutilized. The shell contains chitosan which has many benefits, one of which can lower cholesterol levels. The combination of 2 or more excipients is called co-processed excipients which are then continued into tablets by direct compression. The aim of the study was to find out whether chitosan could be formalized into coprocessed tablets (lactose, primogel, and PEG 4000 7.5% & 15%) by direct compression method and the effect of differences in the characteristics of coprocessed and chitosan tablets with a ratio of PEG 4000 7.5% and 15 % as binder. The evaluation results showed that chitosan tablets fulfilled the requirements for the uniformity of weight, hardness, disintegration time (F1) tests, while they did not meet the requirements for the uniformity of tablet size, friability and disintegration times (F2) tests and the results of the coprocessing evaluation met specifications both F1 and F2, namely: particle size distribution, moisture content, flow rate, angle of repose (very good), compressibility index (adequate) and Hausner's ratio (very good). The evaluation results were then processed statistically using the SPSS application using the independent t-test method which showed that there was no significant difference in the effect of PEG 4000 7.5% and 15% as a binder on the characteristics of co-processed and chitosan tablets. Chitosan tablets from mangrove crab shells (Scylla serrata) cannot be formalized by direct compression with co-processing.

Design of mobile and website health application devices for drug tolerability in hereditary fructose intolerance

BackgroundHereditary fructose intolerance (HFI) is a rare metabolic disease caused by aldolase B deficiency. The aim of our study was to analyse excipient tolerability in patients with HFI and other related diseases and to design mobile and website health applications to facilitate the search for drugs according to their tolerance.ResultsA total of 555 excipients listed in the Spanish Medicines Agency database (July 2023) were classified as suitable for HFI patients, suitable with considerations ((glucose and glucose syrup, intravenous sucrose, oral mannitol, polydextrose, gums and carrageenans, ethanol, sulfite caramel and vanilla), not recommended (intravenous mannitol) and contraindicated (fructose, oral sucrose, invert sugar, sorbitol, maltitol, lactitol, isomaltitol, fruit syrups, honey, sucrose esters and sorbitol esters). Glucose and glucose syrup were classified as suitable with considerations due to its possible fructose content and their potential endogenous fructose production. For other related intolerances, wheat starch was contraindicated and oatmeal was not recommended in celiac disease; oral lactose and lactose-based coprocessed excipient (Cellactose®) were not recommended in lactose intolerance; and glucose, invert sugar and oral sucrose were not recommended in diabetes mellitus. The applications were named IntoMed®. Results are listed in order of tolerability (suitable drugs appear first and contraindicated drugs at the end), and they are accompanied by a note detailing their classified excipients. If a drug contains excipients within different categories, the overall classification will be the most restrictive. The apps are also able to classify substances with the same criteria if they act as active ingredients. The tools exhibited good usability (82.07 ± 13.46 points on the System Usability Scale [range: 0-100]) on a sample of HFI patients, their families and health care professionals.ConclusionsIntoMed® is a tool for finding information about the tolerability of drugs according to excipients for patients with HFI and other related intolerances, with good usability. It is a fast and reliable system that covers the current excipient legislation and expands on it with other specific information: HFI patients should be alert for excipients such as mannitol (especially in intravenous drugs), fruit syrups, honey, sulfite caramel or vanilla. Glucose might contain or produce fructose, and special precaution is needed because of potential errors in their composition.

Development of a novel direct compressible co-processed excipient and its application for formulation of Mirtazapine orally disintegrating tablets

Introduction Orally disintegrating tablets (ODTs) are designed to dissolve in the oral cavity within 3 min, providing a convenient option for patients as they can be taken without water. Direct compression is the most common method used for ODTs formulations. However, the availability of single composite excipients with desirable characteristics such as good compressibility, fast disintegration, and a good mouthfeel suitable for direct compression is limited. Objective This research was proposed to develop a co-processed excipient composed of xylitol, mannitol, and microcrystalline cellulose for the formulation of ODTs. Methods A total of 11 formulations of co-processed excipients with different ratios of ingredients were prepared, which were then compressed into ODTs, and their characteristics were thoroughly examined. The primary focus was on evaluating the disintegration time and hardness of the tablets, as these factors are important in ensuring the ODTs meet the desired criteria. The model drug, Mirtazapine was then incorporated into the chosen optimized formulation. Results The results showed that the formulation comprised of 10% xylitol, 10% mannitol and 80% microcrystalline cellulose demonstrated the fastest disintegration time (1.77 ± 0.119 min) and sufficient hardness (3.521 ± 0.143 kg) compared to the other formulations. Furthermore, the drug was uniformly distributed within the tablets and fully released within 15 min. Conclusion Therefore, the developed co-processed excipients show great potential in enhancing the functionalities of ODTs, offering a promising solution to improve the overall performance and usability of ODTs in various therapeutic applications.

Formulation and Evaluation of Fast-Dissolving Tablets of Losartan Potassium Using Co-Processed Excipients and Statistical Optimisation Using Central Composite Design

Formulation and Evaluation of Fast-Dissolving Tablets of Losartan Potassium Using Co-Processed Excipients and Statistical Optimisation Using Central Composite Design

Co-processed materials testing as excipients to produce Orally Disintegrating Tablets (ODT) using binder jet 3D-printing technology

The use of co-processed materials for Orally Disintegrating Tablets (ODT) preparation by direct compression is well consolidated. However, the evaluation of their potential for ODT preparation by 3D printing technology remains almost unexplored. The present study aimed to estimate the use of commercially available co-processed excipients, conventionally applied in compression protocols, for the preparation of ODTs with binder jetting-3D printing technology. The latter was selected among the 3D printing techniques because the deposition of multiple powder layers allows for obtaining highly porous and easily disintegrating dosage forms. The influence of some process parameters, including layer thickness, type of waveform and spread speed, on the physical and mechanical properties of the prototypes printed were evaluated. Our results suggested that binder jetting-3D printing technology could benefit from the co-processed excipients for the preparation of solid dosage forms. The process optimization conducted with the experiments reported in this work indicated that additional excipients were needed to improve the physical properties of the resulting ODTs.

Segregation of formulated powders in direct compression process and evaluations by small bench-scale testers

Powder segregation can cause severe issues in processes of pharmaceutical drugs for control of content uniformity if the powder is likely to be free or easy flowing. Assessing segregation intensity of formulated powders in a process is challenging at the formulation stage because of the limited availability of samples. An advanced segregation evaluation using small bench-scale testers can be useful for formulation decisions and suggestions of operation conditions in the process, which has not been practically investigated before. In this study, eight formulations (two co-processed excipients blended with one active pharmaceutical ingredient at different ratios) were used for the segregation study on two types of bench-scale testers (air-induced and surface rolling segregation tester), and a pilot simulation process rig as a comparative study. The results show that segregation measured on the bench-scale testers can give a good indication of the segregation intensity of a blend if the segregation intensity is not more than 20%. The comparison also shows that both the bench-scale testers have a good correlation to the process rig, respectively, which means either segregation tester can be used independently for the evaluation. A linear regression model was explored for prediction of segregation in the process.

Development of Novel Tamsulosin Pellet-Loaded Oral Disintegrating Tablet Bioequivalent to Commercial Capsule in Beagle Dogs Using Microcrystalline Cellulose and Mannitol.

In this study, we developed a tamsulosin pellet-loaded orally disintegrating tablet (ODT) that is bioequivalent to commercially available products and has improved patient compliance using microcrystalline cellulose (MCC) and mannitol. Utilizing the fluid bed technique, the drug, sustained release (SR) layer, and enteric layer were sequentially prepared by coating MCC pellets with the drug, HPMC, Kollicoat, and a mixture of Eudragit L and Eudragit NE, respectively, resulting in the production of tamsulosin pellets. The tamsulosin pellet, composed of the MCC pellet, drug layer, SR layer, and enteric layer at a weight ratio of 20:0.8:4.95:6.41, was selected because its dissolution was equivalent to that of the commercial capsule. Tamsulosin pellet-loaded ODTs were prepared using tamsulosin pellets and various co-processed excipients. The tamsulosin pellet-loaded ODT composed of tamsulosin pellets, mannitol-MCC mixture, silicon dioxide, and magnesium stearate at a weight ratio of 32.16:161.84:4.0:2.0 gave the best protective effect on the coating process and a dissolution profile similar to that of the commercial capsule. Finally, no significant differences in beagle dogs were observed in pharmacokinetic parameters, suggesting that they were bioequivalent. In conclusion, tamsulosin pellet-loaded ODTs could be a potential alternative to commercial capsules, improving patient compliance.

Fexofenadine Hydrochloride Dispersible Tablets: A Taste Masking Strategy using Ion Exchange Resin

The pediatric population is more sensitive to allergies. Fexofenadine hydrochloride (FXD-HCL), a non-sedative antihistaminic drug, was chosen to create taste-masked patient-compliant pediatric dispersible tablets. Due to its bitter taste, fexofenadine hydrochloride is unsuitable for the formulation of dispersible tablets; therefore, Kyron T-134®, cation exchange resin was used to form a taste-masked complex with the drug to overcome its bitterness. The FXD HCL-resin complex was prepared using a kneading method and the complexation was confirmed by differential scanning calorimetry and FTIR studies. The FXD HCL-resin complex was evaluated for flow properties, degree of bitterness, assay and release study. Dispersible tablets were formulated by using a co-processed excipient, Granfiller-D211® containing croscarmellose sodium and crosspovidone, microcrystalline cellulose and mannitol. 22 factorial designs with two replicates optimized the dispersible tablets. The tablets, prepared using the direct compression technique on a single-stroke tablet compression machine, were elegant in appearance. Various pre and post-compression tests were conducted on all formulations. The tablets of hardness 3.5 kg/cm2 showed friability, disintegration time, assay within the compendial limit and showed immediate release of a drug (NLT 60% in 10 min and NLT 80% in 30 minutes) in 0.001 N HCl (pH 3). The DSC thermogram indicated partial amorphization of the FXD HCL. Dispersible tablets of fexofenadine hydrochloride and Granfiller-D®211 at 1:4 proportion was stable for one month at ambient and accelerated storage conditions.

Investigating the Impact of Co-processed Excipients on the Formulation of Bromhexine Hydrochloride Orally Disintegrating Tablets (ODTs)

PurposeOrodispersible tablets (orally disintegrating tablets, ODTs) have been used in pharmacotherapy for over 20 years since they overcome the problems with swallowing solid dosage forms. The successful formula manufactured by direct compression shall ensure acceptable mechanical strength and short disintegration time. Our research aimed to develop ODTs containing bromhexine hydrochloride suitable for registration in accordance with EMA requirements.MethodsWe examined the performance of five multifunctional co-processed excipients, i.e., F-Melt® C, F-Melt® M, Ludiflash®, Pharmaburst® 500 and Prosolv® ODT G2 as well as self-prepared physical blend of directly compressible excipients. We tested powder flow, true density, compaction characteristics and tableting speed sensitivity.ResultsThe manufacturability studies confirmed that all the co-processed excipients are very effective as the ODT formula constituents. We noticed superior properties of both F-Melt’s®, expressed by good mechanical strength of tablets and short disintegration time. Ludiflash® showed excellent performance due to low works of plastic deformation, elastic recovery and ejection. However, the tablets released less than 30% of the drug. Also, the self-prepared blend of excipients was found sufficient for ODT application and successfully transferred to production scale. Outcome of the scale-up trial revealed that the tablets complied with compendial requirements for orodispersible tablets.ConclusionsWe proved that the active ingredient cannot be absorbed in oral cavity and its dissolution profiles in media representing upper part of gastrointestinal tract are similar to marketed immediate release drug product. In our opinion, the developed formula is suitable for registration within the well-established use procedure without necessity of bioequivalence testing.

Evaluation of Co-Processed Excipients for Fast Disintegration of Aspirin Tablets Prepared by Direct Compression

Background: Co-processed excipients are popular for direct tablet compression and give added economic value to product formulation. Specific benefits of co-processed excipients include improved flow, compressibility, disintegrating effect, and masking undesirable properties of individual excipients.
 Objective: The aim of this study is to co-process physically modified (pregelatinized) Musa sapientum starch with lactose by fusion and evaluate the effect of the co-processed excipients on the disintegration properties of Aspirin tablet.
 Methods: Co-processed excipients were prepared from pregelatinized Musa sapientium starch and lactose by fusion in ratios of 1:1, 1:2 and 2:1 (BL1, BL2, and BL3 respectively) and evaluated for particle size, pH, moisture content, flow and swelling properties. Aspirin tablets were formulated using the excipients at ratio 5% W/W by direct compression. (FM1, FM2, FM3 respectively). Sodium starch glycolate (FSG) tablet was also prepared as the standard and the formulations were assessed for hardness, friability and disintegration time. Data were analyzed using ANOVA.
 Results: The co-processed excipients possessed excellent flow having a Carr’s index between 18.39-20.78 and Hausner’s ratio ≤ 1.25.BL1 had the highest swelling profile while BL3 had the lowest. Formulation FM1 and FM2 had the highest tensile strength of (0.16 N/cm2). Disintegration time of FM3 (4.28 min) was comparable to that of FSG (4.15 min).
 Conclusion: Co-processing pregelatinized Musa sapientium starch and lactose by fusion influenced tablet disintegration and has potential to be used in manufacture of fast dissolving tablet formulations.

Effect of process parameters in high shear granulation on characteristics of a novel co-processed mesoporous silica material

In this study, insights into the development and optimization of a co-processed excipient based on mesoporous silica are presented. The main advantage of such a material is that it is appropriate for direct tablet compression and has a sufficiently large specific surface area to be suitable for potential subsequent drug loading and formulation of (amorphous) solid dispersions. Our aim was to use a Design of Experiments approach to investigate which process parameters in high shear granulation affect the characteristics of such a co-processed material. The parameters included were the amount of binder (isomalt), the amount of water (granulation liquid), the water addition rate and the speed of the impeller. The responses evaluated and modelled were particle size and its distribution, specific surface area, bulk density, flowability, compressibility and compactibility. The models obtained showed good quality in terms of goodness of fit and predictive power. Active effects were identified for all responses, giving a thorough insight into factors affecting the material characteristics. Optimization experiments resulted in products with the desired characteristics (high specific surface area, large particle size, good flow and compression properties) and confirmed the validity of the generated models.