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Pharmaceutics Jan 2023One of the main challenges to paediatric drug administration is swallowing difficulties, hindering the acceptability of the medicine and hence clinical outcomes. This...
One of the main challenges to paediatric drug administration is swallowing difficulties, hindering the acceptability of the medicine and hence clinical outcomes. This study aims at developing a child-appropriate dosage form, the orodispersible mini-tablet (ODMT), using the model drug carbamazepine (CBZ). This dosage form was prepared and 3D-printed via a semi-solid extrusion technique. Design of Experiment methods were applied for optimising the formulation. The formulation with 40% (/) of SSG (superdisintegrant) and 5% (/) of PVP K30 (binder) was selected and loaded with CBZ. The drug-loaded tablets were characterised by a mean hardness of 18.5 N and a disintegrating time of 84 s, along with acceptable friability. The mean drug loading ratio of the tablets was tested as 90.56%, and the drug release rate in 0.1 M HCl reached 68.3% at 45 min. Excipients showed proper compatibility with the drug in physical form analysis. Taste assessment via an E-tongue was also conducted, where the drug did not show bitter taste signals at a low concentration in the taste assessment, and the sweetener also blocked bitterness signals in the testing. To this end, ODMTs were found to be potential candidates for child-appropriate dosage forms delivering CBZ.
PubMed: 36678881
DOI: 10.3390/pharmaceutics15010250 -
Saudi Pharmaceutical Journal : SPJ :... Feb 2019In this study, we aimed to optimize theophylline pellet formulations using a two-factor three-level full-factorial design (3) by monitoring the concentration of two...
In this study, we aimed to optimize theophylline pellet formulations using a two-factor three-level full-factorial design (3) by monitoring the concentration of two pellet excipients, polyvinyl pyrrolidone K30 (PVP) binder solution (X1) and the hydrophilic excipient mannitol (X2). Their impact on pellet characteristics (responses) were evaluated. Increasing PVP concentration in the binder solution resulted in an increase in the wet mass torque value. The effect of mannitol, however, was antagonistic. Moreover, the pellet particle size was significantly influenced by the level of mannitol, PVP solution, and quadratic effect of mannitol. Mannitol significantly antagonized the pellet particle size. Furthermore, increased mannitol concentrations significantly enhanced drug dissolution rate from the pellets, whereas PVP concentration in the binder solution significantly reduced the drug dissolution rate. In conclusion, wet granulations can be controlled by monitoring the composition of the binder solution and pellet composition.
PubMed: 30766428
DOI: 10.1016/j.jsps.2018.10.002 -
European Journal of Pharmaceutics and... Nov 2022Besides factors such as disintegrant and lubricant, the raw material properties of filler excipients can have an impact on the disintegration behavior of a tablet. The...
Besides factors such as disintegrant and lubricant, the raw material properties of filler excipients can have an impact on the disintegration behavior of a tablet. The current research aims to model the impact of lactose properties on disintegration time. For the first time, the impact of lactose polymorphism, tablet tensile strength, and pore structure parameters on disintegration were evaluated in one study. Six different lactose qualities were compacted into tablets of different solid fractions in a formulation with 5 %w/w diclofenac sodium, 1 %w/w magnesium stearate and 2 %w/w croscarmellose sodium. A linear model was built to identify which parameters impact the disintegration time, using as potential variables the polymorphic composition of the lactose, the porosity, pore size distribution and the tablet tensile strength. The model variables were derived from literature and calibrated with data. After optimization, the model shows a strong correlation (r = 0.982) between measured and predicted disintegration times. Among all investigated variables, the polymorphic composition of lactose, and the pore size distribution have been identified to affect tablet disintegration most. A higher concentration of lactose monohydrate in tablets leads to faster tablet disintegration, explained by the slower dissolution rate of lactose monohydrate compared to anhydrous and amorphous lactose. Tablet tensile strength was not identified as a direct driver for disintegration. Instead, the pore size distribution is a mutual driver for both tablet tensile strength and disintegration. The obtained insights provide guidance on the importance of quality attributes of filler binders for the prediction of tablet disintegration. This study can therefore be used as a starting point for quality-by-design formulation development and for the development of mechanistic models to predict tablet disintegration.
Topics: Lactose; Porosity; Solubility; Tablets; Excipients
PubMed: 36270465
DOI: 10.1016/j.ejpb.2022.10.012 -
International Journal of Pharmaceutical... 2017The delivery of drug is often affected by formulation processes and the excipients used in the formulation.
INTRODUCTION
The delivery of drug is often affected by formulation processes and the excipients used in the formulation.
MATERIALS AND METHODS
A 2 factorial analysis was used in this study to evaluate the effect of acetylated ginger starch (AGS) () as a binder in metronidazole tablets, in comparison to corn starch (CS) BP. The individual and interacting effects of variables (binder type X, binder concentration X, and compression pressure X) used on tablet properties such as friability, crushing strength, crushing strength friability ratio (CSFR), disintegration and crushing strength friability/disintegration time ratio (CSFR/DT) were determined. The effect of these binders on the granule properties using Hausner's ratio, Carr's index (CI), angle of repose, and densities as response parameters was also determined.
RESULTS
Granules prepared with AGS had high densities and small granule sizes when compared with those containing CS. Granules containing CS have better flow properties. X (binder type) has a significant effect on the crushing strength of the tablet. It also had the highest effects on CSFR and CSFR/DT. The combination of XX had the highest effect on crushing strength and DT.
CONCLUSION
This study shows that, in formulations, care must be taken in choosing the excipients and the process parameters required for the formulation since these can affect the delivery of the drug individually or in combination. AGS could be useful as a binder when a tablet with low crushing strength and fast disintegration is desired.
PubMed: 28405575
DOI: 10.4103/jphi.JPHI_31_16 -
Gels (Basel, Switzerland) Mar 2023The plain 5-fluorouracil (5FU) formulations available in the market are associated with adverse effects such as skin irritation, pruritus, redness, blisters, allergy,...
The plain 5-fluorouracil (5FU) formulations available in the market are associated with adverse effects such as skin irritation, pruritus, redness, blisters, allergy, and dryness on the site of application. The objective of the present study was to develop a liposomal emulgel of 5FU with increased skin permeability and efficacy using clove oil and eucalyptus oil along with pharmaceutically acceptable carriers, excipients, stabilizers, binders, and additives. A series of seven formulations were developed and evaluated for their entrapment efficiency, in vitro release profile, and cumulative drug release profile. The compatibility of drugs and excipients, as confirmed by FTIR (fourier-transform infrared spectroscopy) and DSC (differential scanning calorimetry) as well as SEM (scanning electron microscopy) and TEM (transmission electron microscopy) studies, revealed that the size and shape of liposomes are smooth and spherical, and the liposomes are non-aggregated. To understand their efficacy, the optimized formulations were evaluated for cytotoxicity using B16-F10 mouse skin melanoma cells. The eucalyptus oil and clove oil-containing preparation significantly produced a cytotoxic effect against a melanoma cell line. The addition of clove oil and eucalyptus oil increased the efficacy of the formulation by improving skin permeability and reducing the dose required for the anti-skin cancer activity.
PubMed: 36975657
DOI: 10.3390/gels9030209 -
International Journal of Pharmaceutics Dec 2020Cocrystallization of ibuprofen and nicotinamide in hot melt extrusion process has been subject of many studies addressing low ibuprofen bioavailability. However, it is...
Incomplete cocrystalization of ibuprofen and nicotinamide and its interplay with formation of ibuprofen dimer and/or nicotinamide dimer: A thermodynamic analysis based on DFT data.
Cocrystallization of ibuprofen and nicotinamide in hot melt extrusion process has been subject of many studies addressing low ibuprofen bioavailability. However, it is observed that the process of cocrystal formation of ibuprofen and nicotinamide might be incomplete. We hypothesized that formation of dimers of ibuprofen-ibuprofen or dimers nicotinamide- nicotinamide might be the cause of such poor cocrystalization process by altering the phase behaviour of the mixture. This paper addresses the molecular thermodynamics of mixtures of ibuprofen and nicotinamide, with special focus on the possibility of formation of these dimers and their corresponding interplay with mixture phase behaviour. For this purpose, density functional theory calculations are used to calculate electron donor-acceptor sizes on each molecule and accordingly possible dimers of each molecule are analysed. The free energies and phase diagram are determined for (1) when a dimer is formed or (2) no dimer is formed, over a wide operating temperature range of 273.15 K-390 K. The binding and solvation energies are calculated to identify/rank dimers. Calculations showed that formation of dimers requires an energy input which can be accessible noting to the external heating in hot melt extrusion process. The calculated solvation energies of the dimers suggest that addition of liquid binder (water) can mitigate the risk of dimer formations. Addition of proper binder/excipient is an easy route to compensate such dimer formation and to engineer ibuprofen and nicotinamide cocrystallization behaviour.
Topics: Crystallization; Excipients; Ibuprofen; Niacinamide; Thermodynamics
PubMed: 33091551
DOI: 10.1016/j.ijpharm.2020.119992 -
American Journal of Transplantation :... May 2019Microcrystalline cellulose (MCC) is an insoluble material commonly used as a binder and filler in oral medications. Identification of pulmonary intravascular deposition...
Microcrystalline cellulose (MCC) is an insoluble material commonly used as a binder and filler in oral medications. Identification of pulmonary intravascular deposition of MCC in transbronchial biopsies from lung transplant (LT) recipients following parenteral injection of oral medications has only been reported once. A search of our surgical pathology electronic database was performed from January 1, 2000 to November 1, 2017 using the text "transplant transbronchial." The diagnosis field for all cases retrieved was then searched for the text "cellulose." These cases were queried for patient demographics and outcomes. Between January 1, 2000 and November 1, 2017, 1558 lung transplants were performed in 1476 individual patients at our institution; 12 were identified to have MCC in their lung tissue. Patients with MCC identified on biopsies were more likely to be transplanted for cystic fibrosis versus other indications and younger versus older. MCC identified in 2 of our cases was favored to be donor derived. Of the 12 patients, 6 (50%) are deceased. MCC within the pulmonary vasculature may be an indicator of increased complications, mortality, or shortened survival in LT recipients. Detecting intravascular MCC and distinguishing it from aspirated foreign material can be challenging. Awareness of the differential diagnosis for pulmonary foreign material is of paramount importance for the pathologist.
Topics: Administration, Oral; Adolescent; Adult; Biopsy; Cellulose; Cystic Fibrosis; Female; Humans; Infusions, Parenteral; Lung; Lung Diseases; Lung Transplantation; Male; Middle Aged; Pharmaceutical Preparations; Retrospective Studies; Tissue Donors; Young Adult
PubMed: 30725518
DOI: 10.1111/ajt.15286 -
Binder jetting 3D printing of challenging medicines: From low dose tablets to hydrophobic molecules.European Journal of Pharmaceutics and... Jan 2022Increasing access to additive manufacturing technologies utilising easily available desktop devices opened novel ways for formulation of personalized medicines. It is,...
Increasing access to additive manufacturing technologies utilising easily available desktop devices opened novel ways for formulation of personalized medicines. It is, however, challenging to propose a flexible and robust formulation platform which can be used for fabrication of tailored solid dosage forms composed of APIs with different properties (e.g., hydrophobicity) without extensive optimization. This manuscript presents a strategy for formulation of fast dissolving tablets using binder jetting (BJ) technology. The approach is demonstrated using two model APIs: hydrophilic quinapril hydrochloride (QHCl, logP = 1.4) and hydrophobic clotrimazole (CLO, logP = 5.4). The proposed printing method uses inexpensive, well known, and easily available FDA approved pharmaceutical excipients. The obtained model tablets had uniform content of the drug, excellent mechanical properties, and highly porous structure resulting in short disintegration time and fast dissolution rate. The tablets could be scaled and obtained in predesigned shapes and sizes. The proposed method may find its application in the early stages of drug development where high flexibility of the formulation is required and the amount of available API is limited.
Topics: Clotrimazole; Drug Liberation; Excipients; Hydrophobic and Hydrophilic Interactions; Printing, Three-Dimensional; Quinapril; Tablets; Technology, Pharmaceutical
PubMed: 34785345
DOI: 10.1016/j.ejpb.2021.11.001 -
BioMed Research International 2021Polymeric materials from plants continue to be of interest to pharmaceutical scientists as potential binders in immediate release tablets due to availability,...
Polymeric materials from plants continue to be of interest to pharmaceutical scientists as potential binders in immediate release tablets due to availability, sustainability, and constant supply to feed local pharmaceutical industries. Paracetamol tablet formulations were utilized in investigating the potential binding characteristics of pectin harnessed from various okra genotypes (PC1-PC5) in Ghana. The pectin yields from the different genotypes ranged from 6.12 to 18.84%w/w. The pH of extracted pectin ranged from 6.39 to 6.92, and it had good swelling indices and a low moisture content. Pectin extracted from all genotypes were evaluated as binders (10, 15, and 20%w/v) and compared to tragacanth BP. All formulated tablets (F1-F18) passed the weight uniformity, drug content, hardness, and friability tests. Based on their crushing strength, tablets prepared with pectin from the various genotypes were relatively harder ( ≤ 0.05) than tablets prepared with tragacanth BP. Tablets prepared with pectins as binders at 10%w/v and 15%w/v passed the disintegration and dissolution tests with the exception of PC4 at 15%w/v. Incorporation of pectin from all genotypes (excluding PC5) as a binder at concentrations above 15%w/v (F13, F16, F14, and F15) produced tablets which failed the disintegration test and showed poor dissolution profiles. Thus, pectin from these genotypes can be industrially commodified as binders in immediate release tablets using varying concentrations.
Topics: Abelmoschus; Acetaminophen; Chemistry, Pharmaceutical; Excipients; Genotype; Ghana; Pectins; Solubility; Tablets
PubMed: 34888384
DOI: 10.1155/2021/6002286 -
International Journal of Pharmaceutics Jul 2018The overall objective of this work is to understand how excipient characteristics influence the drug product quality attributes and process performance of a continuous... (Comparative Study)
Comparative Study
A novel approach to support formulation design on twin screw wet granulation technology: Understanding the impact of overarching excipient properties on drug product quality attributes.
The overall objective of this work is to understand how excipient characteristics influence the drug product quality attributes and process performance of a continuous twin screw wet granulation process. The knowledge gained in this study is intended to be used for Quality by Design (QbD)-based formulation design and formulation optimization. Three principal components which represent the overarching properties of 8 selected pharmaceutical fillers were used as factors, whereas factors 4 and 5 represented binder type and binder concentration in a design of experiments (DoE). The majority of process parameters were kept constant to minimize their influence on the granule and drug product quality. 27 DoE batches consisting of binary filler/binder mixtures were processed via continuous twin screw wet granulation followed by tablet compression. Multiple linear regression models were built providing understanding of the impact of filler and binder properties on granule and tablet quality attributes (i.e. 16 DoE responses). The impact of fillers on the granule and tablet responses was more dominant compared to the impact of binder type and concentration. The filler properties had a relevant effect on granule characteristics, such as particle size, friability and specific surface area. Binder type and concentration revealed a relevant influence on granule flowability and friability as well as on the compactability (required compression force during tableting to obtain target hardness). In order to evaluate the DoE models' validity, a verification of the DoE models was performed with new formulations (i.e. a new combination of filler, binder type and binder concentration) which were initially not included in the dataset used to build the DoE models. The combined PCA (principle component analysis)/DoE approach allowed to link the excipient properties with the drug product quality attributes.
Topics: Compressive Strength; Drug Compounding; Excipients; Hardness; Particle Size; Pharmaceutical Preparations; Principal Component Analysis; Quality Control; Rheology; Solubility; Surface Properties; Tablets; Technology, Pharmaceutical
PubMed: 29684559
DOI: 10.1016/j.ijpharm.2018.04.017