Solid Dosage Forms Research Articles

Carboxymethyl Starch Films as Enteric Coatings: Processing and Mechanistic Insights

This study proposes the application of carboxymethyl starch derivatives as tablet coatings affording gastro-protection. Carboxymethyl starch (CMS) films were obtained by casting of aqueous filmogenic starch solutions with or without plasticizers and their structural organization was followed using Fourier transform infrared (FTIR), Thermogravimetric analysis (TGA), X-ray diffraction (XRD). Together with data from mechanical tests (tensile strength, elongation, Young's modulus) the results were used to select filmogenic formulations adapted for coatings of tablets. The behaviour of these films was evaluated in simulated gastric and intestinal fluids. The effect of plasticizers (glycerol and sorbitol) on the starch organization, on the rate of drying of the films and on the water vapor absorption was also analyzed. Various types of starch have been compared and the best results were found with high amylose starch (HAS) that was carboxymethylated in an aqueous phase to obtain carboxymethyl high amylose starch (CMHAS). The CMHAS coating solutions containing sorbitol or glycerol as plasticizers have been applied with an industrial pan coater and the final tablets exhibited a good gastro-resistance (up to 2h) in simulated gastric fluid followed by disintegration in simulated intestinal fluid (SIF). The CMHAS derivatives present a high potential as coatings for nutraceutical and pharmaceutical solid dosage forms.

Mechanosynthesis of Stable Salt Hydrates of Allopurinol with Enhanced Dissolution, Diffusion, and Pharmacokinetics.

Allopurinol (ALO) is a medication that treats gout and kidney stones by lowering uric acid synthesis in the blood. The biopharmaceutics classification system (BCS) IV drug exhibits poor aqueous solubility, permeability, and bioavailability. To overcome the bottlenecks of ALO, salts with maleic acid (MLE) and oxalic acid (OXA) were synthesized using the solvent-assisted grinding method. The novel multicomponent solids were characterized by PXRD, DSC, TGA, FT-IR, and SEM images. The crystal structures of these salts with variable stoichiometry were obtained using Rietveld refinement from the high-resolution PXRD data. The proton from the dicarboxylic acid is transferred to the most basic pyrimidine "N" of ALO. The N-H···N hydrogen-bonded ALO homodimer is replaced by the N+-H···O- ionic interactions in ALO-OXA (2:1:0.4) and ALO-MLE (1:1:1) salt hydrates. The organic salts improved solubility and dissolution up to 5-fold and the diffusion permeability up to 12 times compared to the native drug in a luminal pH 6.8 phosphate buffer medium. The salt hydrates were exceptionally stable during storage at 30 ± 5 °C and 75 ± 5% relative humidity. Superior dissolution and diffusion permeability of the ALO-MLE salt resulted in improved pharmacokinetics (peak plasma concentration) that offers a promising solid dosage form with enhanced bioavailability and lower dosage formulation.

Computer numerical control (CNC) carving as an on-demand point-of-care manufacturing of solid dosage form: A digital alternative method for 3D printing

Computer numerical control (CNC) carving is a widely used method of industrial subtractive manufacturing of wood, plastics, and metal products. However, there have been no previous reports of applying this approach to manufacture medicines. In this work, the novel method of tablet production using CNC carving is introduced for the first time. This report provides a proof-of-concept for applying subtractive manufacturing as an alternative to formative (powder compression) and additive (3D printing) manufacturing for the on-demand production of solid dosage forms. This exemplar manufacturing approach was employed to produce patient-specific hydrocortisone (HC) tablets for the treatment of children with congenital adrenal hyperplasia. A specially made drug-polymer cast based on polyethene glycol (PEG 6,000) and hydroxypropyl cellulose was produced using thermal casting. The cast was used as a workpiece and digitally carved using a small-scale 3-dimensional (3D) CNC carving. To establish the ability of this new approach to provide an accurate dose of HC, four different sizes of CNC carved tablet were manufactured to achieve HC doses of 2.5, 5, 7.5 and 10 mg with a relative standard deviation of the tablet weight in the range of 3.69–4.79%. In addition, batches of 2.5 and 5 mg HC tablets met the British Pharmacopeia standards for weight uniformity. Thermal analysis and X-ray powder diffraction indicated that the model drug was in amorphous form. In addition, HPLC analysis indicated a level of purity of 96.5 ± 1.1% of HC. In addition, the process yielded mechanically strong cylindrical tablets with tensile strength ranging from 0.49 to 1.6 MPa and friability values of <1%, whilst maintaining an aesthetic look. In vitro, HC release from the CNC-carved tablets was slower with larger tablet sizes and higher binder contents. This is the first report on applying CNC carving in the pharmaceutical context of producing solid dosage forms. The work showed the potential of this technology as an alternative method for the on-demand manufacturing of patient-specific dosage forms.

Formulation and Evaluation of Mouth Dissolving Film of Imipramine HCL

The main objective of the present study outlines a systematic approach for Design and Evaluation of Fast Dissolving Oral Films of Imipramine HCl to enhance the therapeutic efficacy and provide rapid onset of action in patients suffering from depression Because of patient may have trouble in swallowing a tablet or capsules. Mouth dissolving film is the most advanced oral solid dosage form due to its flexibility and comfort in use. Mouth dissolving films are oral solid dosage form that disintegrate and dissolve within a minute when placed in mouth without taking water or chewing. This dosage form allows the medication to bypass the first pass metabolism so bioavailability of medication may be improved. Fast dissolving Oral film of Imipramine Hydrochloride was formulated by using solvent casting method with different concentrations of HPMC-E3. Film forming property of various grades of HPMC was investigated based on preliminary characteristics of various batches of FDOFs.

Development and validation of a RP-HPLC method for simultaneous determination of Ciprofloxacin and Ornidazole in a solid dosage formulation

Development and validation of a RP-HPLC method for simultaneous determination of Ciprofloxacin and Ornidazole in a solid dosage formulation

Comparation between fluid bed granulation and high shear mixer as a techniques of choice for achieving optimum homogeneity for low dose solid pharmaceutical dosage form

Comparation between fluid bed granulation and high shear mixer as a techniques of choice for achieving optimum homogeneity for low dose solid pharmaceutical dosage form

Risks of Powder Flow Obstruction in Hopper and Bin Discharge in Solid Dosage Form Manufacture should be Predicted Under The Active Stress State

Discharge of powder from a hopper or bin is a common operation in solid dosage form manufacture. Powder flow obstruction during hopper/bin discharge, such as arching or ratholing, remains an outstanding risk and cannot be reliably diagnosed using the existing flow function coefficient-based method. In this study, we showed that the major principal stress (σ1) at the bin outlet is required for an accurate prediction of powder flow obstruction risks. We noted that powder is susceptible to flow obstruction when the unconfined yield strength exceeds the stress facilitating powder failure. We presented a complete model to calculate the stress conditions and subsequently predict flow obstruction risks in hopper/bin discharge based on this criterion. The method was experimentally verified by hopper/bin discharge experiments encompassing 10 powder blends and 2 equipment systems. Importantly, we showed that the active stress state assumption should be employed for the powder flow obstruction prediction because σ1 is high and powder is more susceptible to flow obstruction. Prediction under the passive stress state can lead to significant under-estimation of flow obstruction risks. Therefore, the hopper design protocol, which assumes the passive stress state in arching prediction, should not be indiscriminately used toward pharmaceutical powder flow applications.

Influence of fused deposition modelling printing parameters on tablet disintegration times: a design of experiments study.

Despite the importance of process parameters in the printing of solid dosage forms using fused deposition modelling (FDM) technology, the field is still poorly explored. A design of experiment study was conducted to understand the complete set of process parameters of a custom developed FDM 3D printer and their influence on tablet disintegration time. Nine settings in the Simplify 3D printing process design software were evaluated with further experimental investigation conducted on the influence of infill percentage, infill pattern, nozzle diameter, and layer height. The percentage of infill was identified as the most impactful parameter, as increasing it parabolically affected the increase of disintegration time. Furthermore, a larger nozzle diameter prolonged tablet disintegration, since thicker extruded strands are generated through wider nozzles during the printing process. Three infill patterns were selected for in-depth analysis, demonstrating the clear importance of the geometry of the internal structure to resist mechanical stress during the disintegration test. Lastly, layer height did not influence the disintegration time. A statistical model with accurate fit (R 2 = 0.928) and predictability (Q 2 = 0.847) was created. In addition, only the infill pattern and layer height influenced both the uniformity of mass and uniformity of the disintegration time, which demonstrates the robustness of the printing process.

The importance of compatibility studies in selection of appropriate TiО2 free non-functional film-coating for solid dosage formulation with antioxidant

The importance of compatibility studies in selection of appropriate TiО2 free non-functional film-coating for solid dosage formulation with antioxidant

FTIR Method for Simultaneous determination of Captopril and Hydrochlorothiazid in Raw material and Pharmaceutical Dosage Form

A New FTIR method was developed and validated to simultaneous determination of Captopril (CAP) and Hydrochlorothiazid (HCTZ) in raw material and pharmaceutical dosage forms. The method includes preparation of solid pellets of hydrochlorothiazide and captopril using KBr and the quantitative determination peaks were chosen after conducting an excipient interference study. Then, the validation method was carried out according to the ICH guidelines. The calibration curve was developed using spectral region from 3115.92-3222.1 cm-1 for HCTZ and 1689.91-1800.73 cm-1 for CAP by plotted the peak height (intensity) for the selected peaks against the concentrations where, there are no overlapping with excipients used in the preparation of tablet dosage form. Captopril and Hydrochlorothiazid were detected in the following linear ranges: (0.4-2% w/w) and (0.4-2% w/w); respectively with excellent coefficeients of determination (R2), 0.9989 and 0.9982. Accuracy was found with excellent mean recovery values (98.0–102.0%). The precision showed RSD% was in a satisfactory range (&lt; 2), evidencing the precision of the developed method. In Conclusion this method was inexpensive, environmental friendly and can be employed for simultaneous estimation of CAP and HCTZ in solid dosage forms.

Application of Starch, Cellulose, and Their Derivatives in the Development of Microparticle Drug-Delivery Systems.

Micro- and nanotechnologies have been intensively studied in recent years as novel platforms for targeting and controlling the delivery of various pharmaceutical substances. Microparticulate drug delivery systems for oral, parenteral, or topical administration are multiple unit formulations, considered as powerful therapeutic tools for the treatment of various diseases, providing sustained drug release, enhanced drug stability, and precise dosing and directing the active substance to specific sites in the organism. The properties of these pharmaceutical formulations are highly dependent on the characteristics of the polymers used as drug carriers for their preparation. Starch and cellulose are among the most preferred biomaterials for biomedical applications due to their biocompatibility, biodegradability, and lack of toxicity. These polysaccharides and their derivatives, like dextrins (maltodextrin, cyclodextrins), ethylcellulose, methylcellulose, hydroxypropyl methylcellulose, carboxy methylcellulose, etc., have been widely used in pharmaceutical technology as excipients for the preparation of solid, semi-solid, and liquid dosage forms. Due to their accessibility and relatively easy particle-forming properties, starch and cellulose are promising materials for designing drug-loaded microparticles for various therapeutic applications. This study aims to summarize some of the basic characteristics of starch and cellulose derivatives related to their potential utilization as microparticulate drug carriers in the pharmaceutical field.

An Overview of Oral Thin Film Drug Delivery Systems with Fast Dissolving Films

Fast-dissolving oral thin films (OTFs), rather than tablets, are the product of choice for many pharmaceutical businesses. The benefits of tablets (precise dose, simple administration) and liquid dosage forms (easily swallowed, quick bioavailability) are all present in films. Four out of five patients, according to statistics, prefer orally disintegrating dose forms over traditional solid oral dosage forms. Children, the elderly, people who are bedridden, people who are emetic, and those who have CNS illnesses have trouble swallowing or digesting solid dose forms. Many of these individuals refuse to take solid dose forms because they are afraid of choking. OTFs are immediately moistened by saliva when put on the tongue's tip or base. Because of this, OTFs quickly hydrate before dissolving or disintegrating to release the drug for local or systemic absorption. This technology offers a solid foundation for the creation of patent-compliant items and for extending the patent protection of currently available goods. Fast-dissolving oral thin films can be used for a variety of purposes, including gastroprotective and sublingual delivery systems in addition to buccal fast-dissolving systems. This study emphasizes the composition, detailing the numerous natural and synthetic polymer kinds, diverse manufacturing processes, packaging materials, and assessment tests for OTFs.

Popping balls papaya extract: Preparation of pediatric dosages in therapeutic formulations for therapeutic usage in dengue and malaria

Spherification is a cutting-edge molecular gastronomy method that has just emerged in the realm of food science and technology, and it may be used to produce foods with superior sensory qualities and a high level of consumer acceptance and satisfaction. This method is excellent for making semi-solid spheres with a membrane coating so thin that it is barely discernible when placed in the mouth. This experiment used a simple spherification method to turn papaya extract into popping balls with sodium alginate. Intraventricular haemorrhage is a potentially fatal consequence of thrombocytopenia in the newborn period. Extracts from papaya leaves show promise as a treatment for refractory cases of newborn thrombocytopenia. This research aims to learn how to make popping balls out of papaya extract that are both safe to eat and tasty by adding jaggery as a sweetener. Physical parameters such as pH, viscosity, and stability of the prepared balls were studied in in-vitro, 30-day time frame. The findings revealed that papaya-popping balls are homogeneous and have a low viscosity. The expected drug release was 91%. Papaya popping balls were subjected to a three-month stability study. According to the results, there was no variation in colour, pH, or viscosity during the study. All the particles in the formulation were round so that it may be given to kids as an alternative to oral solid dose forms.

Bahan Tambahan dalam Sediaan Tablet: Review

Tablets are solid pharmaceutical dosage form without or with suitable excipients by press or compression manufacturing process. The excipient chosen can influence the product performance (physical properties and stability) and bioavailability. All excipients must be optimally selected to get the optimal formula of tablet dosage form. This article review aims to overview of excipient in tablet dosage form and their role in formulating tablet dosage form. this review article was written based on literature studies from electronic databases such as PubMed, ScienceDirect, and Google Scholar which contain related information using keyword in Indonesian or English use article published in 2013-2023. excipients in tablet dosage form are fillers or diluents, disintegrants, lubricants, preservatives, flavors, sweeteners, coloring, and coating agents. These excipients added to tablet dosage form to facilitating the process of manufacture tablet dosage form, increasing stability and effectiveness of active pharmaceutical ingredients in tablet. The conclusion of this review, there are many classification of tablet excipients which is different function to get compendial requirements of tablet dosage form.

A Review on Mouth Dissolving Tablet

Nowadays, dysphagia is an issue with traditional dosage forms like tablets and capsules, which leads to a high prevalence of non-compliance and renders therapy ineffective. Mouth dissolving tablets, which have good hardness, dose homogeneity, and ease of administration and serve as the preferred option of dosage form for paediatrics, geriatrics, and travelling patients, have been designed to eliminate the issues associated with conventional dosage forms. In order to have enough hardness, integrity, and speed up disintegration without water, the MDTs were invented. rapid dissolution Without the use of water, tablets easily dissolve or disintegrate in saliva. Some tablets are truly fast-dissolving tablets because they are made to dissolve in saliva amazingly quickly—within a few seconds. Others have additives that speed up the process of Tablet disintegration in the oral cavity is more properly referred to as fast-disintegrating tablets because it can take them up to a minute to do so. This tablet shape was created to make it possible to administer an oral solid dose form without drinking any liquids. These tablets easily dissolve or break down in the saliva, usually in under 60 seconds.

Continuous Manufacturing of Solvent-Free Cyclodextrin Inclusion Complexes for Enhanced Drug Solubility via Hot-Melt Extrusion: A Quality by Design Approach.

Conventional cyclodextrin complexation enhances the solubility of poorly soluble drugs but is solvent-intensive and environmentally unfavorable. This study evaluated solvent-free hot-melt extrusion (HME) for forming cyclodextrin inclusion complexes to improve the solubility and dissolution of ibuprofen (IBU). Molecular docking confirmed IBU's hosting in Hydroxypropyl-β-cyclodextrin (HPβ-CD), while phase solubility revealed its complex stoichiometry and stability. In addition, an 11 mm twin-screw co-rotating extruder with PVP VA-64 as an auxiliary substance aided the complex formation and extrusion. Using QbD and the Box-Behnken design, we studied variables (barrel temperature, screw speed, and polymer concentration) and their impact on solubility and dissolution. The high polymer concentration and high screw speeds positively affected the dependent variables. However, higher temperatures had a negative effect. The lowest barrel temperature set near the Tg of the polymer, when combined with high polymer concentrations, resulted in high torques in HME and halted the extrusion process. Therefore, the temperature and polymer concentration should be selected to provide sufficient melt viscosities to aid the complex formation and extrusion process. Studies such as DSC and XRD revealed the amorphous conversion of IBU, while the inclusion complex formation was demonstrated by ATR and NMR studies. The dissolution of ternary inclusion complexes (TIC) produced from HME was found to be ≥85% released within 30 min. This finding implied the high solubility of IBU, according to the US FDA 2018 guidance for highly soluble compounds containing immediate-release solid oral dosage forms. Overall, the studies revealed the effect of various process parameters on the formation of CD inclusion complexes via HME.

Absolute and Relative Bioavailability of Oral Solid Dosage Formulations of Deucravacitinib in Humans.

itinib is an oral, selective, allosteric inhibitor of tyrosine kinase 2, an intracellular signaling kinase involved in the pathogenesis of immune-mediated inflammatory diseases. The absolute and relative bioavailability (BA) were evaluated in phase 1, open-label studies in healthy adults to assess (1) the absolute BA of the deucravacitinib tablet formulation following single oral administration of a 12-mg tablet and an intravenous microdose infusion of 0.1-mg carbon-13 and nitrogen-15-labeled deucravacitinib ([13 C2 , 15 N3 ] deucravacitinib) solution in 8 subjects, and (2) the relative oral BA of deucravacitinib tablet and capsule formulations at the 3- and 12-mg dose levels in 20 subjects. The absolute oral availability of deucravacitinib in the tablet formulation was near complete at approximately 99%. The total clearance (254mL/min) was low relative to hepatic blood flow, and volume of distribution (∼140L) was greater than total body water, indicating extravascular distribution. Deucravacitinib systemic exposure (maximum plasma concentration, area under the plasma drug concentration curve from time zero to the time of the last quantifiable nonzero concentration, and area under the plasma drug concentration-time curve from time zero extrapolated to infinity) after administration of the tablet formulation were similar to the capsule at the tested 3- and 12-mg doses. In both studies, deucravacitinib was safe with no clinically relevant changes in laboratory values, electrocardiogram parameters, or vital signs.

Synthesis, characterisation and quantification of the new psychoactive substance 1-(1,3-benzodioxol-5-yl)-2-(propylamino)butan-1-one (bk-PBDB, putylone)

Synthetic cathinones are a continually evolving family of illicit drugs, with novel analogues frequently being detected. This paper reports the detection of 1-(1,3-benzodioxol-5-yl)-2-(propylamino)butan-1-one, bk-PBDB (putylone), within solid dosage forms (tablets) seized by law enforcement for the first time in the United Kingdom. The identity of the compound was confirmed via the synthesis of a pure bk-PBDB reference standard and direct spectral comparison by 1H NMR and GC-EI-MS analysis. A full analytical profiling of bk-PBDB by nuclear magnetic resonance (NMR), attenuated total reflection Fourier-transform infrared (FTIR) spectroscopy and gas chromatography-electron ionisation-mass spectrometry (GC-EI-MS) is reported and shows good concordance between the seized sample and the reference standard. A validated GC-EI-MS method for the routine quantification of the cathinone in bulk forensic samples (LOD: 0.09 μg/mL, LOQ: 0.26 μg/mL) was also developed and using this method, the seized tablets were determined to contain a mixture of bk-PBDB (130.6–135.5 mg/tablet) and caffeine (40.2–43.4 mg/tablet) respectively.

Pediatric and Geriatric-Friendly Buccal Foams: Enhancing Omeprazole Delivery for Patients Encountering Swallowing Difficulties

Buccal foams containing omeprazole (OME) have been developed as potential drug delivery systems for individuals encountering swallowing difficulties, particularly pediatric and geriatric patients. The buccal foams were formulated from lyophilized aqueous gels of maltodextrin, used as a sweetener, combined with various polymers (alginate, chitosan, gelatin, tragacanth) to fine tune their structural, mechanical, and physicochemical properties. Consistent with the requirements for efficient drug delivery across buccal epithelium, the foam comprised of hydroxypropyl methylcellulose and alginate (HPMC-Alg-OME), exhibited moderate hardness and high mucoadhesion resulting to prolonged residence and increased transport of the active across porcine epithelium. The HPMC-Alg-OME foam induced a 30-fold increase in the drug's apparent permeability across porcine buccal tissue, compared to the drug suspension. The developed buccal foams exhibited excellent stability, as evidenced by the unchanged omeprazole content even after six months of storage under ambient conditions (20 °C and 45% RH). Results indicate that buccal foams of omeprazole may address the stability and ease of administration issues related to oral administration of the drug, particularly for children and elderly patients who have difficulty swallowing solid dosage forms.

Controlling release from encapsulated drug-loaded devices: insights from modeling the dissolution front propagation.

Dissolution of drug from its solid form to a dissolved form is an important consideration in the design and optimization of drug delivery devices, particularly owing to the abundance of emerging compounds that are extremely poorly soluble. When the solid dosage form is encapsulated, for example by the porous walls of an implant, the impact of the encapsulant drug transport properties is a further confounding issue. In such a case, dissolution and diffusion work in tandem to control the release of drug. However, the interplay between these two competing processes in the context of drug delivery is not as well understood as it is for other mass transfer problems, particularly for practical controlled-release considerations such as an encapsulant layer around the drug delivery device. To address this gap, this work presents a mathematical model that describes controlled release from a drug-loaded device surrounded by a passive porous layer. A solution for the drug concentration distribution is derived using the method of eigenfunction expansion. The model is able to track the dissolution front propagation, and predict the drug release curve during the dissolution process. The utility of the model is demonstrated through comparison against experimental data representing drug release from a cylindrical drug-loaded orthopedic fixation pin, where the model is shown to capture the data very well. Analysis presented here reveals how the various geometrical and physicochemical parameters influence drug dissolution and, ultimately, the drug release profile. It is found that the non-dimensional initial concentration plays a key role in determining whether the problem is diffusion-limited or dissolution-limited, whereas the nature of the problem is largely independent of other parameters including diffusion coefficient and encapsulant thickness. We expect the model will prove to be a useful tool for those designing encapsulated drug delivery devices, in terms of optimizing the design of the device to achieve a desired drug release profile.