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1.
Chem Pharm Bull (Tokyo) ; 72(4): 374-380, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38599850

RESUMO

Tablets are the most commonly used dosage form in the pharmaceutical industry, and their properties such as disintegration, dissolution, and portability are influenced by their strength. However, in industry, the mixing fraction of powders to obtain a tablet compact with sufficient strength is determined based on empirical rules. Therefore, a method for predicting tablet strength based on the properties of a single material is required. The objective of this study was to quantitatively evaluate the relationship between the compression properties and tablet strength of powder mixtures. The compression properties of the powder mixtures with different plasticities were evaluated based on the force-displacement curves obtained from the powder compression tests. Heckel and compression energy analyses were performed to evaluate compression properties. During the compression energy analysis, the ratio of plastic deformation energy to elastic deformation energy (Ep/Ee) was assumed to be the plastic deformability of the powder. The quantitative relationship between the compression properties and tensile strength of the tablets was investigated. Based on the obtained relationship and the compression properties of a single material, a prediction equation was put forward for the compression properties of the powder mixture. Subsequently, a correlation equation for tablet strength was proposed by combining the values of K and Ep/Ee obtained from the Heckel and compression energy analyses, respectively. Finally, by substituting the compression properties of the single material and the mass fraction of the plastic material into the proposed equation, the tablet strength of the powder mixture with different plastic deformabilities was predicted.


Assuntos
Química Farmacêutica , Química Farmacêutica/métodos , Pós , Resistência à Tração , Comprimidos , Pressão , Composição de Medicamentos
2.
Int J Mol Sci ; 23(19)2022 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-36232785

RESUMO

The biogenetic law (recapitulation law) states that ontogenesis recapitulates phylogenesis. However, this law can be distorted by the modification of development. We showed the recapitulation of phylogenesis during the differentiation of various cell types, using a meta-analysis of human single-cell transcriptomes, with the control for cell cycle activity and the improved phylostratigraphy (gene dating). The multipotent progenitors, differentiated from pluripotent embryonic stem cells (ESC), showed the downregulation of unicellular (UC) genes and the upregulation of multicellular (MC) genes, but only in the case of those originating up to the Euteleostomi (bony vertebrates). This picture strikingly resembles the evolutionary profile of regulatory gene expansion due to gene duplication in the human genome. The recapitulation of phylogenesis in the induced pluripotent stem cells (iPSC) during their differentiation resembles the ESC pattern. The unipotent erythroblasts differentiating into erythrocytes showed the downregulation of UC genes and the upregulation of MC genes originating after the Euteleostomi. The MC interactome neighborhood of a protein encoded by a UC gene reverses the gene expression pattern. The functional analysis showed that the evolved environment of the UC proteins is typical for protein modifiers and signaling-related proteins. Besides a fundamental aspect, this approach can provide a unified framework for cancer biology and regenerative/rejuvenation medicine because oncogenesis can be defined as an atavistic reversal to a UC state, while regeneration and rejuvenation require an ontogenetic reversal.


Assuntos
Células-Tronco Pluripotentes Induzidas , Neoplasias , Animais , Biologia , Diferenciação Celular/genética , Células-Tronco Embrionárias , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Medicina Regenerativa
3.
Pharm Dev Technol ; 27(7): 805-815, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36047995

RESUMO

The novel modulus-based approach was developed to characterize the compression behavior of the materials and how it results into tablet mechanical strength (TMS) of the final tablet. The force-displacement profile for the model materials (Vivapur® 101, Starch 1500®, Emcompress®, and Tablettose® 100) was generated at different compression pressures (100, 150, and 200 MPa) and speeds (0.35, 0.55, and 0.75 m/s) using compaction emulator (Presster™). A generated continuous compression profile was evaluated with Heckel plot and the proposed material modulus method. The computed compression parameters were qualitatively and quantitatively correlated with TMS by principal component analysis and principal component regression, respectively. Compression modulus has negatively correlated, while decompression modulus is positively correlated to TMS. Proposed modulus descriptors are independent of particle density measurements required for the Heckel method and could overcome the limitations of the Heckel method to evaluate the decompression phase. Based on the outcome of the study, a two-dimensional compression and decompression modulus classification system (CDMCS) was proposed. The proposed CDMCS could be used to define critical material attributes in the early development stage or to understand reasons for tablet failure in the late development stage.


Assuntos
Química Farmacêutica , Amido , Química Farmacêutica/métodos , Descompressão , Pós , Comprimidos , Resistência à Tração
4.
AAPS PharmSciTech ; 21(7): 242, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32839881

RESUMO

Liquisolid technology, as a promising approach for bioavailability enhancement, has received increasing attention in recent years. However, literature reports addressing the challenges for its industrial application, particularly those related to compaction behavior of liquisolid systems, are scarce. The aim of this study was to investigate the influence of process parameters and formulation variables on the flowability, wetting, and compaction properties of the liquisolid systems prepared in a fluid bed processor. The experiments with microcrystalline cellulose, as a carrier, were performed according to 23 full factorial design. The effects of liquid content, spray air pressure, and liquid feed rate on the properties of liquisolid systems were investigated. Liquisolid admixtures with microcrystalline cellulose were compared with those prepared with novel carriers, Fujicalin® and Neusilin® US2. "Out-die" Heckel, modified Walker, and Kuentz-Leuenberger models were used to analyze the compressibility of liquisolid admixtures. The results obtained showed that an increase in liquid content (in the range of 10 to 15%) led to a decrease in flowability of liquisolid admixtures with microcrystalline cellulose, as well as more pronounced influence of spraying conditions. On the other hand, higher liquid content led to higher compressibility. Fujicalin® and Neusilin® US2 liquisolid admixtures were found to have superior flowability and compressibility in comparison with those with microcrystalline cellulose, despite the considerably higher liquid load (50-55% liquid content in Neusilin® US2 compacts). Acceptable compactibility of the investigated liquisolid systems was observed. The fluid bed processor was shown to be suitable equipment for production of liquisolid systems, but with careful adjustment of process parameters.


Assuntos
Composição de Medicamentos/métodos , Celulose/química , Química Farmacêutica , Excipientes/química , Solubilidade , Comprimidos/química
5.
AAPS PharmSciTech ; 21(5): 186, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32638170

RESUMO

The effect of storage condition (% RH) on flufenamic acid:nicotinamide (FFA:NIC) cocrystal compressibility, compactibility, and tabletability profiles was not observed after visual evaluation or linear regression analysis. However, multivariate statistical analysis showed that storage condition had a significant effect on each compressional profile. Shapiro and Heckel equations were used to determine the compression parameters: porosity, Shapiro's compression parameter (f), densification factor (Da), plastic yield pressure (YPpl), and elastic yield pressure (YPel). Latent variable models such as exploratory factor analysis, principal component analysis, and principal component regression were employed to decode complex hidden main, interaction, and quadratic effects of % RH and the compression parameters on FFA:NIC tablet mechanical strength (TMS). Statistically significant correlations between f and Da, f and YPpl, and Da and YPel supported the idea that both rearrangement and fragmentation, and plastic deformation are important to FFA:NIC TMS. To the authors knowledge, this is the first time that simultaneously operating dual mechanisms of fragmentation and plastic deformation in low and midrange compression, and midrange plastic deformation have been identified and reported. A quantitative PCR model showed that f, Da, and YPel had statistically significant main effects along with a significant antagonist storage condition-porosity "conditional interaction effect". f exhibited a 2.35 times greater impact on TMS compared to Da. The model root-mean-square error at calibration and prediction stages were 0.04 MPa and 0.08 MPa, respectively. The R2 values at the calibration stage and at the prediction stage were 0.9005 and 0.7539, respectively. This research demonstrated the need for caution when interpreting the results of bivariate compression data because complex latent inter-relationships may be hidden from visual assessment and linear regression analysis, and result in false data interpretation as illustrated in this report.


Assuntos
Química Farmacêutica , Pressão , Modelos Químicos , Análise Multivariada , Tamanho da Partícula , Porosidade , Análise de Componente Principal , Análise de Regressão , Comprimidos , Resistência à Tração
6.
Drug Dev Ind Pharm ; 44(9): 1512-1519, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29734848

RESUMO

OBJECTIVE: The objective of this study was to evaluate non-crystalline cellulose (NCC) as a novel tablet excipient in solid oral dosage forms in comparison with microcrystalline cellulose (MCC) and silicified microcrystalline cellulose (Prosolv®, SMCC). SIGNIFICANCE: MCC, although a widely used tablet excipient, has diasdvantages in terms of its low dilution potential for potent drugs, and sensitivity to lubricant and moisture. SMCC, a modified version of MCC, has improved tablet compression properties. However, SMCC is expensive and also affects the moisture sorption and particle deformation during compression leading to increased tensile strength and tablet hardness. NCC was found to be similar to SMCC in its performance as a tablet excipient and thus can serve as a cheaper alternative to SMCC. METHODS: Scanning electron microscopy (SEM), X-ray diffrectometry (XRD), and differential scanning calorimetry (DSC) analyses were performed on NCC, MCC, and SMCC. Further, out-of-the die Heckel, Kawakita compact densification and stress-strain analyses were performed to evaluate their compaction and compressibility properties. Various compendial and non-compendial tests were performed to to determine the flow properties of materials. Dissolution studies were performed using amlodipine besylate as a marker drug. RESULTS: It was found that NCC has similar or even better flow properties and compactibility than MCC due to its porous and amorphous structure whereas it had similar properties as SMCC. CONCLUSIONS: Based on the data, it can be concluded that NCC can serve as a cheaper and better alternative to MCC as excipient in solid dosage forms.


Assuntos
Anlodipino/química , Celulose/química , Excipientes/química , Dureza/efeitos dos fármacos , Porosidade/efeitos dos fármacos , Pressão , Solubilidade/efeitos dos fármacos , Comprimidos/química , Resistência à Tração/efeitos dos fármacos
7.
Drug Dev Ind Pharm ; 44(11): 1770-1782, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29968491

RESUMO

CONTEXT: Knowledge of the effects of high-shear granulation process parameters and scale-up on the properties of the produced granules is essential for formulators who face challenges regarding poor flow and compaction during development of modified release tablets based on high-molecular weight hypromellose (hydroxypropylmethylcellulose (HPMC)) polymers. Almost none of the existing studies deal with realistic industrial formulation. OBJECTIVE: The aim was to investigate the effects of scale-up and critical process parameters (CPPs) of high-shear granulation on the quality attributes of the granules, particularly in terms of the flow and compaction, using a realistic industrial formulation based on HPMC K100M polymer. METHODS: The flow properties were determined using flow time, Carr index, tablet mass, and crushing strength variations. The compaction properties were quantified using the 'out-of-die' Heckel and modified Walker models, as well as the tensile strength profile and elastic recovery. High-shear granulation was performed at different scales: 4 L, 300 L, and 600 L. RESULTS AND CONCLUSION: The scale itself had larger effects on the granule properties than the CPPs, which demonstrated high robustness of formulation on the individual scale level. Nevertheless, to achieve the desired flow and compaction, the values of the CPPs need to be precisely selected to fine-tune the process conditions. The best flow was achieved at high volumes of water addition, where larger and more spherical granules were obtained. The CPPs showed negligible influence on the compaction with no practical implications, however, the volume of water addition volume was identified as having the largest effects on compaction.


Assuntos
Derivados da Hipromelose , Comprimidos , Tecnologia Farmacêutica , Composição de Medicamentos , Peso Molecular , Tamanho da Partícula , Resistência à Tração
8.
Pharm Dev Technol ; 23(10): 1108-1116, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29310491

RESUMO

The objective of the present study was to investigate the influence of processing methods on the physical and mechanical properties of formulations containing Ibuprofen and HPC-SSL. The powder blends, containing Ibuprofen and HPC-SSL in ratio of 9:0.5, were processed using melt granulation (MG) by hot melt extrusion (HME) and wet granulation (WG) by high shear mixer. Formulated granules and powder blends were compressed into round flat faced tablets using Riva Piccola tablet press. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) studies proved that granulation process did not significantly alter the crystallinity of Ibuprofen, however, particle density and flow properties were significantly improved. Scanning electron microscopy (SEM) and particle size analysis corroborate with the findings that the flow characteristics of granules from MG were relatively superior to other formulations. Formulations were investigated for out-of-die compaction behaviour using Heckel, Kawakita, and CTC profile analysis. Detailed examination revealed that all three formulations differed in particle size due to the granulation, thus conferring to different compaction behaviour. In WG and MG, granulation offered an increase in particle size resulting in high compressibility along with deformation at low compression pressure. This results into low yield pressure, low yield strength, and higher densification, as compared with dry blend. The current work provides an insight into factors affecting physical and mechanical properties tablets, which can facilitate the rational selection of suitable change in processing method instead of changing excipients.


Assuntos
Anti-Inflamatórios não Esteroides/química , Celulose/análogos & derivados , Composição de Medicamentos/métodos , Excipientes/química , Ibuprofeno/química , Celulose/química , Cristalização , Tamanho da Partícula , Difração de Pó , Pós , Solubilidade , Comprimidos , Difração de Raios X
9.
AAPS PharmSciTech ; 18(4): 1293-1301, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27480443

RESUMO

The present investigation was carried out to develop and characterize a multifunctional co-processed excipient for improving the compressibility of poorly compressible drugs. Etodolac was used as a model drug. Microcrystalline cellulose (MCC), lactose monohydrate (lactose), and StarCap 1500 (StarCap) were selected as components of the co-processed excipient. The spray drying method was used for co-processing of excipients. D-optimal mixture design was applied to optimize the proportion of component excipients. Statistical analysis of the D-optimal mixture design revealed that all response variables were significantly affected by the independent variables (p value < 0.05). Optimized composition was obtained from the desirability function. The optimized composition of the co-processed excipient was found to be 30% MCC, 25% lactose, and 45% StarCap. This optimized batch was evaluated for flow properties, compressibility parameters such as Kawakita's and Kuno's equation and Heckel's equation, and dilution potential. Evaluation parameters for flow properties (angle of repose, Carr's index, and Hausner's ratio) suggested excellent flow character. The parameters of Kawakita's and Kuno's equation and Heckel's equation suggested improvement in the compressibility of the model drug. Dilution potential was found to be 40%, and based on that, tablets of the model drug were formulated and evaluated for general evaluation parameters of tablets. All the parameters were found to be within the acceptance criteria which concluded that the multifunctional directly compressible co-processed excipient was prepared successfully that improved the compressibility of the poorly compressible model drug etodolac along with spray drying as an efficient method for the preparation of co-processed excipient.


Assuntos
Excipientes/química , Comprimidos , Tecnologia Farmacêutica , Celulose/química , Etodolac , Lactose/química , Comprimidos/química
10.
Drug Dev Ind Pharm ; 42(11): 1877-86, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27094181

RESUMO

CONTEXT: Information about flow and compaction properties of hypromellose (HPMC) polymers is essential for the technologists who are facing challenges regarding poor flow and compaction while developing new controlled release matrix tablets. There is a profound lack of studies in this field and none of the published ones deal with the compaction of the newly introduced HPMC grades specifically designed for direct compression (DC). OBJECTIVE: The objective behind this study was the evaluation of flow and compaction properties of six different grades of HPMC substitution type 2208 polymers, including two second generation directly compressible grades from Dow Chemical Company (K100LV, K15M, K4M CR, K4M DC, K100M CR and K100M DC). METHODS: Flow properties were determined using flow time and Carr index. Compaction properties were quantified using "out-of-die" Heckel and modified Walker models as well as tensile strength profile and elastic recovery. We used statistical approach to analyze the results. RESULTS AND CONCLUSION: Due to larger, rounder and smoother particles both DC grades showed distinctly better flow properties compared to their non-DC counterparts. Overall, K15M showed the best compaction properties, closely followed by K100LV. K100M grades showed superior compaction properties over K4M grades. The new, second generation DC grades had poorer compaction properties, however, they exhibited better flow properties on the other hand. Considering all compaction results, the Heckel model gave better description of compressibility compared to the Walker model, so it may be preferred in case of studying HPMC polymers and other similar materials.


Assuntos
Metilcelulose/química , Polímeros/química , Comprimidos/química , Resistência à Tração/fisiologia , Tamanho da Partícula , Pressão , Solubilidade
11.
Pharmaceutics ; 16(3)2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38543256

RESUMO

Using microcrystalline cellulose (MCC) with plastic behaviour and calcium phosphate anhydrous (CaHPO4) with brittle behaviour under compaction is very popular in the pharmaceutical industry for achieving desirable structural-mechanical properties of tablet formulations. Thus, mixtures of specific grades of MCC and CaHPO4 were tested in volume proportions of 100-0, 75-25, 50-50, 25-75, and 0-100 at a constant weight-by-weight concentration of sodium stearyl fumarate lubricant, utilizing a state-of-the-art benchtop compaction simulator (STYL'One Nano). Tablet formulations were prepared at 100, 150, 250, 350, 450, and 500 MPa, and characterized by tabletability profile, ejection force profile, proportion-tensile strength relationship, proportion-porosity relationship, pressure-displacement, and elastic recovery profiles, as well as by in-/out-of-die Heckel plots and yield pressures. Interestingly, the 25-75 formulation demonstrated a two-stage out-of-die Heckel plot and was additionally investigated with X-ray micro-computed tomography (µCT). By post-processing the µCT data, the degree of brittle CaHPO4 particles falling apart, along with the increasing compression pressure, was quantified by means of the surface area to volume (S/V) ratio. For the 25-75 formulation, the first stage (up to 150 MPa) and second stage (above the 150 MPa) of the out-of-die Heckel plot could be attributed to predominant MCC and CaHPO4 deformation, respectively.

12.
Eur J Pharm Biopharm ; 192: 1-12, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37716476

RESUMO

During tablet manufacturing an increase in the production temperature can lead to an alteration of tablet characteristics. In the present study, the influence of the initial particle size on the tableting behavior of ductile polymers upon temperature rise was investigated. Different grades of the respective materials were tableted at temperatures ranging from 22 to 70 °C. Alterations in tableting behavior were affected by the initial particle size. Smaller particle sizes led to a more pronounced decrease in yield pressure and net work of compaction during compressibility analysis. The results were confirmed in the tabletability studies. Tablets from binary mixtures with lactose containing smaller polymer particles yielded a stronger increase in tensile strength. Differences in the tensile strength increase of two grades from the same material correlated with the ratio of their median particle sizes. The alteration of compactibility profiles was also particle size dependent. The increase in solid fraction was more prominent for binary mixtures containing polymers with smaller particle sizes. However, the ratio of the median particle sizes of the compared grades showed no systematic effect. The results underline the importance of controlling the structural properties of a material carefully during formulation development and production. If a formulation responds to temperature variations, an increase in particle size might be beneficial to decrease its heat sensitivity.


Assuntos
Excipientes , Temperatura Alta , Tamanho da Partícula , Excipientes/química , Polímeros , Comprimidos/química , Resistência à Tração , Composição de Medicamentos
13.
Pharmaceutics ; 15(4)2023 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-37111721

RESUMO

The aim of this feasibility study was to investigate the possibility of producing industrial-scale relevant, robust, high drug-loaded (90.9%, w/w) 100 mg dose immediate-release tablets of isoniazid and simultaneously meet the biowaiver requirements. With an understanding of the real-life constrictions on formulation scientists during product development for the generic industry, this study was done considering a common set of excipients and manufacturing operations, as well as paying special attention to the industrial-scale high-speed tableting process as one of the most critical manufacturing operations. The isoniazid substance was not applicable for the direct compression method. Thus, the selection of granulation method was logically justified, and it was fluid-bed granulated with an aqueous solution of Kollidon® 25, mixed with excipients, and tableted with a rotary tablet press (Korsch XL 100) at 80 rpm (80% of the maximum speed) in the compaction pressure range 170-549 MPa monitoring of ejection/removal forces, tablet weight uniformity, thickness, and hardness. Adjusting the main compression force, the Heckel plot, manufacturability, tabletability, compactability, and compressibility profiles were analysed to choose the main compression force that resulted in the desirable tensile strength, friability, disintegration, and dissolution profile. The study showed that highly robust drug-loaded isoniazid tablets with biowaiver requirements compliance can be prepared with a common set of excipients and manufacturing equipment/operations incl. the industrial-scale high-speed tableting process.

14.
Int J Pharm ; 627: 122205, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36122616

RESUMO

A parameterization of compaction simulator generated dynamic compression profile with a few grams of powder provides important information about the material deformation and compact elasticity. The Heckel equation is by far the most popular choice among pharmaceutical scientists for such parametrization. A general approach of Heckel analysis uses pycnometric powder density (ρP0) for relative density calculation. However, as 'in-die' tablet bulk density at applied compression pressure (ρBP) becomes greater than or equal to the measured ρP0, the general approach typically poses a negative porosity challenge at high compression pressure regions. It is only theoretically possible to have a tablet with zero or negative porosity. Negative porosity may be detected during 'in-die' compression analysis, but it will not exist after ejection of the tablet in practical aspect. Thus, the present work proposes a new approach to using pycnometric tablet density (ρPP) in the relative density calculations of Heckel analysis. This ρPP may be a better representation of actual tablet particle volume, as it is composed of non-accessible intra-particulate pores, which are broken under applied compression pressure. A new approach showed its immunity for Heckel high-pressure negative porosity. It enables the utilization of the compression and decompression phases of dynamic compression profiles to evaluate macroscopic compaction performance. The proposed approach was validated with a reported modified Heckel approach. The Heckel parameters computed with both methodologies for microcrystalline cellulose and lactose were not statistically different. However, a modified Heckel approach was unable to compute Heckel parameters of poorly compacting starch unlike the new approach. A modified Heckel approach became invalid during starch compaction at low compression pressures (below 400 MPa), where starch was forming weaker but still intact tablets. Certainly, a complete Heckel profiling with a new approach could save time and costs in an early development stage for designing and screening scientifically based lead prototype formulations.


Assuntos
Lactose , Tecnologia Farmacêutica , Porosidade , Pós , Tecnologia Farmacêutica/métodos , Comprimidos , Amido
15.
Pharmaceutics ; 14(5)2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35631499

RESUMO

The present study focuses on the compaction behavior of polymeric excipients during compression in comparison to nonpolymeric excipients and its consequences on commonly used Heckel analysis. Compression analysis at compaction pressures (CPs) from 50 to 500 MPa was performed using a compaction simulator. This study demonstrates that the particle density, measured via helium pycnometer (ρpar), of polymeric excipients (Kollidon®VA64, Soluplus®, AQOAT®AS-MMP, Starch1500®, Avicel®PH101) was already exceeded at low CPs (<200 MPa), whereas the ρpar was either never reached for brittle fillers such as DI-CAFOS®A60 and tricalcium citrate or exceeded at CPs above 350 MPa (FlowLac®100, Pearlitol®100SD). We hypothesized that the threshold for exceeding ρpar is linked with predominantly elastic deformation. This was confirmed by the start of linear increase in elastic recovery in-die (ERin-die) with exceeding particle density, and in addition, by the applicability in calculating the elastic modulus via the equation of the linear increase in ERin-die. Last, the evaluation of "density under pressure" as an alternative to the ρpar for Heckel analysis showed comparable conclusions for compression behavior based on the calculated yield pressures. However, the applicability of Heckel analysis for polymeric excipients was questioned in principle. In conclusion, the knowledge of the threshold provides guidance for the selection of suitable excipients in the formulation development to mitigate the risk of tablet defects related to stored elastic energy, such as capping and lamination.

16.
Int J Pharm X ; 3: 100094, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34458719

RESUMO

Despite the ability to characterize the plasticity of powders in a material-sparing and expedited manner, the in-die Heckel analysis has been widely criticized for its sensitivity to several factors, such as particle elastic deformation, tooling size, lubrication, and speed. Using materials exhibiting a wide range of mechanical properties, we show that the in-die P y correlates strongly with three established plasticity parameters obtained from the out-of-die Heckel analysis, Kuentz-Leuenberger analysis, and macroindentation. Thus, the in-die P y is a reliable parameter for quantifying powder plasticity in a material-sparing and expedited manner.

17.
Int J Pharm ; 608: 121110, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34547394

RESUMO

The aim of this systematic study was to analyze the granulometric and rheological behavior of tableting mixtures in relation to tabletability by single tablet and lab-scale batch compression with an eccentric tablet machine. Three mixtures containing 33, 50, and 66% of the cohesive drug paracetamol were prepared. The high compressibility of the powder mixtures caused problems with overcompaction or lamination in the single tablet compression method; due to jamming of the material during the filling of the die, the lab-scale batch compression was impossible. Using high shear granulation, the flow properties and tabletability were adjusted. A linear relationship between the span of granules and the specific energy measured by FT4 powder rheometer was detected. In parallel, a linear relationship between conditioned bulk density and the tensile strength of the tablets at lab-scale batch tableting was noted. The combination of dynamic image analysis and powder rheometry was useful for predicting the tabletability of pharmaceutical mixtures during the single tablet (design) compression and the lab-scale batch compression.


Assuntos
Acetaminofen , Composição de Medicamentos , Tamanho da Partícula , Pós , Reologia , Comprimidos , Resistência à Tração
18.
Eur J Pharm Biopharm ; 153: 23-35, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32504797

RESUMO

Drug-drug cocrystals (DDC) represent a unique subset of pharmaceutical materials offering distinct advantages in combination therapies, pharmacokinetics, and patient compliance. However, their structure-function relationships are rarely reported despite its central importance in successful medicine. A material-sparing approach consisting of a molecular and structural perspective is reported to evaluate tabletability of a model DDC, metformin:salicylic acid, relative to its components: metformin HCl (MET) and sodium salicylate (SAL). MET alone displayed a very poor tabletability, which could be attributed to its isotropic and stiff interaction topology. SAL displayed a highly anisotropic interaction topology with layers of strongly hydrogen-bonded salicylate molecules promoting deformation and tabletability. This is also confirmed by its low moduli. DDC yielded intermediate stiffness and elastic anisotropy material with an improved plastic flow and overall better tabletability. Overall, DDC is a promising therapeutic class requiring the physical-mechanical evaluation to assure their processability to enjoy their therapeutic advantages.


Assuntos
Metformina/química , Ácido Salicílico/química , Comprimidos/química , Anisotropia , Cristalização/métodos , Relação Estrutura-Atividade
19.
Curr Drug Deliv ; 17(6): 523-539, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32384027

RESUMO

BACKGROUND: Developing a new excipient and obtaining its market approval is an expensive, time-consuming and complex process. Compared to that, the co-processing of already approved excipients has emerged as a more attractive option for bringing better characteristic excipients to the market. The application of the Design of Experiments (DoE) approach for developing co-processed excipient can make the entire process cost-effective and rapid. OBJECTIVE: The aim of the present investigation was to demonstrate the applicability of the DoE approach, especially 32 full factorial design, to develop a multi-functional co-processed excipient for the direct compression of model drug - cefixime trihydrate using spray drying technique. METHODS: The preliminary studies proved the significant effect of atomization pressure (X1) and polymer ratio (microcrystalline cellulose: mannitol - X2) on critical product characteristics, so they were selected as independent variables. The angle of repose, Carr's index, Hausner's ratio, tensile strength and Kuno's constant were selected as response variables. RESULT: The statistical analysis proved a significant effect of both independent variables on all response variables with a significant p-value < 0.05. The desirability function available in Design Expert 11® software was used to prepare and select the optimized batch. The prepared co-processed excipient had better compressibility than individual excipients and their physical mixture and was able to accommodate more than 40 percent drug without compromising the flow property and compressibility. CONCLUSION: The present investigation successfully proved the applicability of 32 full factorial design as an effective tool for optimizing the spray drying process to prepare a multi-functional co-processed excipient.


Assuntos
Antibacterianos/química , Cefixima/química , Celulose/química , Composição de Medicamentos , Humanos , Manitol/química , Resistência à Tração
20.
Int J Pharm ; 563: 237-248, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-30935917

RESUMO

In this work, lignin was spray dried with sodium lauryl sulphate (SLS) in order to improve the compaction properties of lignin. Bulk level and physicochemical properties of spray dried formulations were measured and compared to as-received lignin and lactose which was used as a reference excipient. Single component tablets from individual powders were prepared and the mechanical properties of these powders were investigated by analysing force-displacement curves recorded during tableting, using a series of compaction equations. Moreover, the performance of these excipients in binary blends containing an active pharmaceutical ingredient (API) was investigated. A positive effect of SLS on the mechanical properties and bulk level properties of the spray dried formulations was observed. Spray dried formulations containing SLS showed superior flow properties to pure spray dried lignin while retaining similar particle size distributions. Spray dried formulations containing up to 10 w/w% SLS also showed superior compactibility in binary blends to as-received materials at porosity levels relevant for immediate release tablets. This study highlights the importance of understanding the compaction mechanics of single component powders as a means of predicting their behaviour in multi-component blends.


Assuntos
Composição de Medicamentos/métodos , Excipientes/química , Lignina/química , Dodecilsulfato de Sódio/química , Tensoativos/química , Dessecação/métodos , Tamanho da Partícula , Pós
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