Development Of Solid Dosage Forms Research Articles

Archaeosomes for Oral Drug Delivery: From Continuous Microfluidics Production to Powdered Formulations

Archaeosomes were manufactured from natural archaeal lipids by a microfluidics-assisted single-step production method utilizing a mixture of di- and tetraether lipids extracted from Sulfolobus acidocaldarius. The primary aim of this study was to investigate the exceptional stability of archaeosomes as potential carriers for oral drug delivery, with a focus on powdered formulations. The archaeosomes were negatively charged with a size of approximately 100 nm and a low polydispersity index. To assess their suitability for oral delivery, the archaeosomes were loaded with two model drugs: calcein, a fluorescent compound, and insulin, a peptide hormone. The archaeosomes demonstrated high stability in simulated intestinal fluids, with only 5% of the encapsulated compounds being released after 24 h, regardless of the presence of degrading enzymes or extremely acidic pH values such as those found in the stomach. In a co-culture cell model system mimicking the intestinal barrier, the archaeosomes showed strong adhesion to the cell membranes, facilitating a slow release of contents. The archaeosomes were loaded with insulin in a single-step procedure achieving an encapsulation efficiency of approximately 35%. These particles have been exposed to extreme manufacturing temperatures during freeze-drying and spray-drying processes, demonstrating remarkable resilience under these harsh conditions. The fabrication of stable dry powder formulations of archaeosomes represents a promising advancement toward the development of solid dosage forms for oral delivery of biological drugs.

Nanoparticle-releasing xerogel films prepared by a one-step method

Aggregation remains a challenge in the development of solid dosage forms of nanoparticles. Herein, we investigated whether xerogel films can allow sustained release of nanoparticles encapsulating curcumin (as a model drug) while preventing their aggregation. Such films can be fabricated by casting nano-oil droplets in an aqueous solution. In this study, curcumin and poly (lactic-co-glycolic acid) (PLGA) were dissolved in methylene chloride and emulsified in a polyvinyl alcohol (PVA)-propylene glycol (PG) solution. While drying the cast, the nano-oil droplets solidified to form nanoparticles. Concurrently, the PVA-PG solution was gelatinated and further dried to form a xerogel. The xerogel film containing curcumin-loaded nanoparticles disintegrated in vitro within 10 min, releasing the nanoparticles without aggregation. The emitted nanoparticles in turn released curcumin at a first-order rate over 90 min. Thus, xerogel films containing nanoparticles could be useful sustained-release solid preparations for delivering nanoparticles at a controlled rate without aggregation.

Preparation and investigation of properties of resveratrol and solubilizers compositions

Background. The search for technology or the use of excipients for the development of drugs containing poorly soluble pharmaceutical substances is an urgent task of pharmacy. According to the biopharmaceutical classification system, resveratrol belongs to group 4: the substance has low solubility and low permeability. Therefore, one of the priorities in the development of drugs with resveratrol is to increase its solubility and, as a result, increase its permeability. The article presents the results of physicochemical studies of resveratrol compositions with solubilizers (poloxamer 407, polysorbate 80, methyl-beta-cyclodextrin) after dissolution in a common solvent followed by evaporation.Aim. Obtaining compositions of resveratrol with solubilizers and auxiliary formations with an exclusive study of their properties for the development of solid dosage forms.Materials and methods. Trans-resveratrol, poloxamer 407, polysorbate 80, methyl-beta-cyclodextrin, citric and ascorbic acids, glycerin, methanol; high performance liquid chromatography, differential scanning calorimetry.Results. Physical and chemical studies of the obtained compositions of resveratrol with excipients were carried out. Excipients used: citric and ascorbic acids for all compositions, as well as glycerin for compositions with tween 80. Stability studies were carried out under conditions of «accelerated aging», as a result of which a noticeable decrease in the amount of resveratrol was found (80 % of the original). Studies of the stability of resveratrol have shown that at low pH, inherent in the stomach, its content remains practically unchanged for two days. And at pH close to neutral, the content of resveratrol is reduced to 90 % of the original amount. The obtained results indicate the feasibility of developing drugs that promote the absorption of resveratrol in the stomach and are stored at low temperatures (in the refrigerator).Conclusion. Compositions of resveratrol with solubilizers were obtained and the choice of excipients for the development of solid dosage forms was substantiated. Recommendations are given for obtaining solid dosage forms for each of the developed formulations and storage conditions are determined.

Preparation, characterization, and crystal structures of novel sophocarpine salts with improvements on stability and solubility

Crystal engineering has proved to be an effective and reliable approach to tailor the physicochemical properties of active pharmaceutical ingredients. In this work, three novel sophocarpine salts were prepared and reported, named sophocarpine-hesperetin (SC-HES), sophocarpine-L-(-) malic acid monohydrate (SC-LMA MH), and sophocarpine-p-hydroxybenzoic acid monohydrate (SC-PHBA MH). The crystal structures of the salts were confirmed by infrared spectroscopy and single crystal X-ray diffraction. SC-HES exhibited a laminated molecular stacking structure, SC-LMA MH formed a wavy layered structure, while sophocarpine molecules filled in the voids of the reticular structure to form the 3D structure of the SC-PHBA MH. Thermal analysis shows that after salification, the melting point of the compound increased from 78°C to over 120°C, overcoming its low melting point. Lattice energy and Hirshfeld surface analysis indicated that lower lattice energy provides better thermal stability of the crystal and intermolecular hydrogen bonds (O–H···O and N→H···O) play a key role in the construction of the crystal structures. In addition, the water solubility and hygroscopicity of the three salts were characterized and discussed, with SC-HES exhibiting satisfying physical stabilities and hygroscopicity, and SC-LMA MH achieving 6.7 times solubility than the free base, which provides viable options for solid dosage form development of the drug.

How Does Long-Term Storage Influence the Physical Stability and Dissolution of Bicalutamide from Solid Dispersions and Minitablets?

The stability of amorphous drugs is among the main challenges in the development of solid dosage forms. This paper examines the effect of storage conditions (25 °C/60% RH and 40 °C/75% RH) and different packaging materials, i.e., polystyrene containers and PVC/Al blisters, on the crystallinity and dissolution characteristics of solid dispersions containing bicalutamide and polyvinylpyrrolidone. The results confirmed drug amorphization upon milling and improved dissolution resulting from the lack of a crystal lattice. These properties varied with time regarding sample composition, storage conditions, and packaging material. The most resistant to storage conditions was the 1:1 solid dispersion packed into blisters. Based on the obtained results, the 1:1 solid dispersion was formulated into minitablets, which were then tested after tableting and then packed into PVC/Al blisters and stored for six months in the same conditions as solid dispersions. We proved that efficient stabilization of amorphous bicalutamide depends on the barrier properties of packaging materials and that a properly chosen material protected the drug substance from the influence of unfavorable storage conditions such as elevated temperature and humidity.

An IQ Consortium Perspective on Connecting Dissolution Methods to In Vivo Performance: Analysis of an Industrial Database and Case Studies to Propose a Workflow

Assessment of bioperformance to inform formulation selection and development decisions is an important aspect of drug development. There is high demand in the pharmaceutical industry to develop an efficient and streamlined approach for better understanding and predicting drug product performance to support acceleration of clinical timelines. This manuscript presents an effort from the IQ Formulation Bioperformance Prediction Working Group composed of members from 12 pharmaceutical companies under the IQ Consortium to develop a database around the topic of formulation bioperformance prediction and report findings from the database analysis. Six case studies described in the manuscript demonstrate how bioperformance models were used to predict in vivo performance and to provide guidance addressing questions encountered during oral solid dosage form development. The case studies also described findings of a correlation between in vitro dissolution and in vivo performance and how dissolution data can be incorporated into physiologically based biopharmaceutical modeling. Finally, a workflow for how in vitro dissolution data can be utilized to predict clinical bioperformance of oral solid dosage forms is proposed.

Evaluation on physicochemical properties and stability of Thanaka bark powder for natural face powder products

Thanaka (Hesperethusa crenulata Roem.) has been traditionally applied as cosmetics in Myanmar and the northern of Thailand [1] and exhibited anti-oxidant, anti-inflammatory, anti-microbial, skin lightening, and sun protection properties [1-4]. Thanaka’s specifications for cosmetic development are sparse to be presented, although its flowability was reported [1]. Of which, the bark was more suitable than the stem for solid dosage form development [1]. Thus, this study was aimed to assess the physicochemical properties and stability of Thanaka bark powder. The yellowish light brown powder (L* = 75.63 ± 0.01, a* = 5.58 ± 0.02 and b* = 23.45 ± 0.02) (Figure 1A) with bulk and tapped densities of 0.25 ± 0.00 and 0.29 ± 0.00 g/mL, was able to absorb water and oil (17.31 ± 0.77% and 13.39 ± 0.29%). The powder was ICP-MS proved to be uncontaminated with heavy metals prohibited for cosmetics. The powder morphology was plate-like crystals with fractured as SEM observed (Figure 1B). Thermal properties examined by DSC resulted in glass transition, crystallization and melting temperatures of 66.43, 70.25 and 73.39°C, with 51.32 ± 4.13% of crystallinity by XRD. The color (ΔE ≤ 1.43 ± 0.04), morphology, thermal properties, water absorption capacity and oil absorption capacity slightly shifted following to 3-month storage under ambient temperature and 45°C.

The choice of excipients and optimization of the composition of orally disintegrating tablets based on paracetamol and N-acetyl-D-glucosamine

Aim. The choice of the qualitative and quantitative composition of excipients to provide the required mechanical strength and disintegration time when developing a pharmaceutical composition in the form of orally disintegrating tablets (ODT) based on paracetamol and N-acetyl-D-glucosamine. Materials and methods. The study object was pharmaceutically accepted excipients used in the pharmaceutical development of solid dosage forms. To conduct the statistical analysis of experimental data, a Minitab® 19.1.1 software was used. Results and discussion. The excipients (povidone of different brands, copovidone, crospovidone of different brands, croscarmellose) used when developing ODT were considered, and it was determined that copovidone and crospovidone type A showed the most optimal quality indicators of the composition. It was found that the particle sizeof crospovidone and the route of its introduction affected the rate of disintegration in the aqueous medium. Using the method of mathematical prediction the optimal content of excipients in the composition and the experimental confirmation ofthe quality indicators of the mixture selected to create ODT were determined. Conclusions. Excipients used in the development of ODT have been considered, and the excipients exhibiting the best quality indicators of the compositions have been found. Both the influence of the particle size of crospovidone, and the route of its administration have been determined. The optimal content of excipients in the composition and their experimental confirmation have been determined due to mathematical prediction.

Tehnika istraživanja i analize podataka primenjena u analizi istorijskih podataka

Understanding the effect of the characteristics of formulation and process parameters on the physicochemical properties of a pharmaceutical product is very significant for the development of solid dosage forms, as the knowledge gained on small scale batches in the early phase of development is used in the later phases of product lifecycle or in the development of other products. One of the approaches for gaining a better understanding of the effects of the formulation and production process on the quality of the finished product is to apply a systematical approach which concerns performing experiments according to a predefined factorial or fractional factorial experimental plan. However, often it is the case that there are available data gathered in a non-systematic way, because experiments were not performed according to a predetermined experimental plan. In such a case, data mining techniques could be used to extract useful data from the historical data set. In this research, the possibility of using several data mining techniques to build models that describe the effect of formulation characteristics on acid resistance and dissolution profile of a model drug from gastro-resistant pellets. The model drug used in the research is duloxetine hydrochloride from the group of antidepressants. It belongs to the BCS 2 class of active pharmaceutical ingredients, and it is therefore necessary for the release profile of duloxetine to be characterized by a higher number of tested time points. The developed models can be used for planning future laboratory trials, or in the development of other products.

Pregled i kritička analiza matematičkih pristupa za karakterizaciju praškova i višečestičnih sistema u razvoju lekova

An understanding of material properties and processing effects on solid dosage forms performance is required within the Quality-by-design approach to pharmaceutical development. Several research groups have developed mathematical approaches aiming to facilitate the selection of formulation composition and the manufacturing technology. These approaches are based on material particulate, bulk and compression-related properties. This paper provides theoretical assumptions and a critical review of different mathematical approaches for processability characterization of powders and multiparticulate units. Mathematical approaches have mainly been developed for directly compressible materials, but sometimes other manufacturing technologies, such as roller compaction and wet granulation, are also considered. The obtained compact tensile strength has been implemented in the majority of approaches, as an important characteristic describing compact mechanical properties. Flowability should be also evaluated, since it affects sample processability. Additionally, particle size and shape, material density and compressibility, compactibility and tabletability profiles have been also distinguished as relevant properties for solid dosage form development. The application of mathematical approaches may contribute to the mechanistic understanding of critical material attributes and facilitate dosage form development and optimization. However, it is essential to select the appropriate one, based on the intended dosage form characteristics, in order to ensure that all relevant powder/multiparticulate units characteristics are implemented and critically evaluated.

Determination of technological parameters of powder masses of the propolis phenolic hydrophobic drug, grape seeds, bitter chestnut seeds and their mixtures in solid dosage forms

An important task in the course of pharmaceutical development of solid dosage forms is to determine a set of technological methods and study the technological parameters of the powders under research for the purpose of further encapsulation or tabletting of substances with different physicochemical characteristics. Aim. To study the main technological parameters of the standardized substance of the propolis phenolic hydrophobic drug (PPHD), grape seeds, bitter chestnut seeds and their mixtures for the purpose of their further introduction into the capsules with the anti-inflammatory and venotonic action developed. Materials and methods. The pharmaco-technological studies of AFI powder masses (fluidity, angle of repose, bulk density, etc.) were performed in accordance with the requirements of the State Pharmacopoeia of Ukraine and scientific and practical sources of literature. Results and discussion. The tests performed indicate that the substances studied and their mixtures do not have satisfactory pharmaco-technological properties, are characterized by a low value of fluidity and the ability to absorb moisture during storage. Conclusions. The results of the research conducted confirm the need to add certain groups of excipients in the powder mass for their further encapsulation and the use of appropriate technological methods when developing oral dosage forms.

Development of Fully Redispersible Dried Nanocrystals by Using Sucrose Laurate as Stabilizer for Increasing Surface Area and Dissolution Rate of Poorly Water-Soluble Drugs

There is much interest in converting poorly water-soluble drugs into nanocrystals as they provide extremely high surface area that increases dissolution rate and oral bioavailability. However, nanocrystals are prepared as aqueous suspensions, and once the suspensions are dried for development of solid dosage forms, the nanocrystals agglomerate as large particles to reduce the excess surface energy. For successful development of drug products, it is essential that any agglomeration is reversible, and the dried nanocrystals regain original particle sizes after redispersion in aqueous media. We have established that sucrose laurate serves as a superb stabilizer to ensure complete redispersion of dried nanocrystals in aqueous media with mild agitation. Nanocrystals (150–300 nm) of three neutral drugs (fenofibrate, danazol and probucol) were produced with sucrose laurate by media milling, and suspensions were dried by tray drying under vacuum, spray drying, and lyophilization. Dried solids and their tablets redispersed into original particle sizes spontaneously. Preliminary studies showed that sucrose laurate can also redisperse acidic and basic drugs, indicating its versatile application. Fatty acid ester of another disaccharide, lactose laurate, also performed like sucrose laurate. Thus, we have developed a method of retaining high dissolution rate and, by implication, high bioavailability of nanocrystals from solid formulations.

DEVELOPMENT OF OPTIMAL COMPOSITION FORMULATION OF RESVERATROL AND SOLUBILISERS

Introduction. Increasing of poorly soluble pharmaceutical substances bioavailability is one of important problems of pharmaceutical technology. Resveratrol is a plant origin polyphenol with a broad spectrum of biological effects. However, due to poor solubility and, as a result, low bioavailability, it is not promising for the development of oral drugs. Thus, today resveratrol is presented only as a biologically active substance that is component of biologically active food supplements.The objective of the research is selection of the optimal solubilizer to increase the solubility of resveratrol by determining the solubilization parameters.Materials and methods. The spectrophotometric characteristics of resveratrol were studied using three groups of solubilizers: poloxamers, polysorbates and cyclodextrins. Studies were carried out in 50 mM hydrochloric acid buffer(pH 1.2) and 50 mM phosphate buffer(pH 6.8). Spectrophotometric measurements were carried out on a spectrophotometer UV/VIS-3600 Shimadzu (Japan) in the wavelength range of 220–380 nm. The effect of solubilizers on the spectrophotometric characteristics of resveratrol was determined in buffer solutions containing the solubilizer and resveratrol in significantly less concentration of its own solubility in water. The used multiple excess of the solubilizer ensured the finding of all resveratrol in a solubilized form. During the determining parameters of solubilization, buffer solutions containing from 2 to 10 mM solubilizers were added to the obviously excess of resveratrol. The indicated amount of resveratrol ensured the presence of its precipitate in all experimentsto determine the completeness of solubilization of the studied polyphenol.Results. Based on the obtained spectrophotometric characteristics of solubilizers solutions with resveratrol, the most effective for the further development of solid dosage forms for oral administration are poloxamer 407, polysorbate 80 and modified methyl-beta-cyclodextrin, which ensure complete dissolution of resveratrol when its content in the composition with a solubilizer is about 10 %.Conclusion. Based on the data obtained on the spectrophotometric characteristics of resveratrol using solubilizers, it can be argued that it is possible to create drugs with improved solubility of the studied polyphenol. On the basis of its compositions with poloxamer 407, polysorbate 80 and modified methyl-beta-cyclodextrin, with the selection of appropriate excipients, solid dosage forms for oral intake can be developed.

Effect of Counterions on Dissolution of Amorphous Solid Dispersions Studied by Surface Area Normalized Dissolution.

Solubility enhancement has become a common requirement for formulation development to deliver poorly water soluble drugs. Amorphous solid dispersions (ASDs) and salt formation have been two successful strategies, yet there are opportunities for further development. For ASDs, drug-polymer phase separation may occur at high drug loadings during dissolution, limiting the increase of drug loadings in ASD formulations. For salt formation, a salt form with high crystallinity and sufficient solid-state stability is required for solid dosage form development. This work studied the effect of counterions on the dissolution performance of ASDs. Surface area normalized dissolution or intrinsic dissolution methodology was employed to eliminate the effect of particle size and provide a quantitative comparison of the counterion effect on the intrinsic dissolution rate. Using indomethacin (IMC)-poly(vinylpyrrolidone-co-vinyl acetate) ASD as a model system, the effect of different bases incorporated into the ASD during preparation, the molar ratios between the base and IMC, and the drug loadings in the ASD were systematically studied. Strong bases capable of ionizing IMC significantly enhanced drug dissolution, while a weak base did not. A physical mixture of a strong base and the ASD also enhanced the dissolution rate, but the effect was less pronounced. At different base to IMC molar ratios, dissolution enhancement increased with the base to IMC ratio. At different drug loadings, without a base, the IMC dissolution rate decreased with the increase of drug loading. After incorporating a strong base, it increased with the increase of drug loading. The observations from this study were thought to be related to both the ionization of IMC in ASDs and the increase of microenvironment pH by the incorporated bases. With the significant enhancement of the drug dissolution rate, our work provides a promising approach of overcoming the dissolution limitation of ASD formulations at high drug loadings.

Investigation into liquisolid system processability based on the SeDeM Expert System approach

Liquisolid systems are emerging formulation approach for poorly soluble drugs, based on adsorption/absorption of drug dispersion and obtaining free-flowing powder with good compressibility. SeDeM Expert System represents a powder processability evaluation method. It may provide additional insight into liquisolid systems critical quality attributes, but the contribution of this approach remains to be explored. The aims of this study were: pellet preparation by combination of liquisolid technology and water granulation/extrusion, evaluation of liquisolid based systems (pellets/admixtures) and investigation into the applicability of SeDeM Expert System in liquisolid systems characterization. Pellets/admixtures were prepared with microcrystalline cellulose as carrier and crospovidone/silicon dioxide as coating agent. Ibuprofen solution in polyethylene glycol 400 was used as liquid phase. After comprehensive sample characterization, experimentally obtained parameters were mathematically transformed and evaluated in the SeDeM Expert System framework.Pellets exhibited low aspect ratio and excellent flowability, despite liquid load up to 52.2%. The investigated liquisolid admixtures exhibited good flowability and faster drug dissolution than pellets. Single pellet crushing test results exhibited strong correlation with compact indentation hardness and may be used as indentation hardness predictor. SeDeM Expert System provides useful insight into liquisolid system processability and comparative evaluation and it may facilitate final solid dosage form development.

Alteration of crystallinity and thermal properties from incompatibility between ibuprofen and boundary lubricants

Lubricant is an essential compound for pharmaceutical formulation since it is often required to ensure the success of pharmaceutical manufacturing especially tablet compression and capsule filling process. Most lubricants used in pharmaceutical industry are boundary lubricants. The most commonly used boundary lubricants are metallic salts of fatty acids such as magnesium stearate and stearic acid. However, other lubricants, including fatty acid esters, inorganic materials and polymers have been used in the cases when stearic acid and metallic salts of fatty acids do not meet the performance expectation. In this study, stearic acid, magnesium stearate, aluminium monostearate and glyceryl dibehenate were chosen as the boundary lubricants whereas ibuprofen (IBU) was employed as the model drug. The aims of this study are to investigate the incompatibility between IBU and these boundary lubricants and to observe the alteration of crystallinity and thermal properties with differential scanning calorimetry (DSC), hot stage microscopy (HSM) and powder X-ray diffraction (PXRD) techniques. The eutectic formation between IBU and all boundary lubricants was revealed with DSC, PXRD and HSM techniques. The thermal properties of individual substance and all physical mixture (PM) between IBU and lubricants from DSC analysis were confirmed with the HSM technique. The partial melting temperature (PMT) and complete melting temperature (CMT) observed from HSM were close to the thermal parameters obtained from DSC results. Moreover, FT-IR spectra indicated an interaction between IBU and boundary lubricants via hydrogen bonding since the vibrational frequency in the region 1700–1400 cm−1 shifted to lower value. This understanding of alteration of crystallinity and thermal properties from incompatibility between compounds is beneficial for pharmaceutical solid dosage form development.

The crystal packing and slip plane analysis in mechanical properties improvement of mefenamic acid by cocrystallization with nicotinamide coformer

Mefenamic acid is an analgesic non-steroidal anti-inflammatory drug (NSAID) that is categorized as Biopharmaceutical Classification System (BCS) class II drug. Cocrystallization of mefenamic acid (MFA) with nicotinamide (NIC) has been reported to enhance the solubility of MFA for about 2.56 times higher than pure MFA. As a part of MFA-NIC development in pharmaceutical dosage form, we reported the improvement of mechanical properties of MFA-NIC cocrystal based on the presence of slip planes in crystal structure. The research was initially by synthesizing and characterizing the cocrystal by using X-ray diffraction analysis, and was followed by the investigation of the mechanical properties of MFA and its cocrystal, i.e. tensile strength and deformation parameter. The correlation of crystal structure with mechanical properties was determined by crystal packing motif and slip plane analysis from single crystal data by using Mercury 3.6. The tensile strength of MFA was acceptance at 20.0 MPa, and dropped at more than 25.0 MPa. A better tableting performance was observed in MFA-NIC cocrystal which had the tensile strength 1.5 times higher than MFA at 12.5 MPa and gradually increased with an increasing pressure up to 2.5 times at 22.5 MPa. The flat slip plane of MFA-NIC cocrystal was predicted as the key factor in the improvement of its mechanical properties, compared to zigzag slip plane of MFA. In conclusion, MFA-NIC cocrystal had the better mechanical properties than pure MFA due to its flat slip plane and it becomes potential to be explored in further development of solid dosage form.

Polymer-Assisted Aripiprazole-Adipic Acid Cocrystals Produced by Hot Melt Extrusion Techniques.

Pharmaceutical cocrystals are a promising strategy to increase the solubility and dissolution rate of poorly soluble drugs. However, their manufacturing process requires a large quantity of solvents. The present study aimed to produce cocrystals by a solvent-free hot melt extrusion (HME) method to improve their solubility and dissolution rate. Aripiprazole (ARP) and adipic acid (ADP) were used as a weakly basic drug and acidic coformer, respectively. The processability of a plain ARP-ADP physical mixture (PM) compared with a PM with 5% Soluplus® (SOL) was investigated. Incorporating 5% SOL into the ARP-ADP blend reduced the processing torque and improved processability. The effects of temperature and screw speed on the formation of cocrystals were studied, and cocrystals were characterized by differential scanning calorimetry (DSC), fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, powder X-ray diffraction (PXRD), scanning electron microscopy, and hot-stage microscopy. FTIR spectra revealed noncovalent interaction between ARP and ADP, which was confirmed by NMR spectra. Similarly, PXRD data exhibited characteristic peaks confirming the formation of new crystalline material. Further, the results indicated that cocrystals demonstrated higher dissolution rates and improved compressibility, as well as enhanced flow characteristics compared with pure ARP, suggesting its suitability in the development of solid dosage forms.

Traditional and Advanced Flow Characterization Techniques: A Platform Review for Development of Solid Dosage Form

Preformulation studies like storage, transfer, fluidisation, and compaction, are subject to the excellent flowability of the powder. It is often required for proper operational management and consistent design of industrial processes. Two basics methods have been utilised to characterise the flow behaviour of bulk solids. Traditionally, powder has been evaluated in terms of simple and straight forward techniques like Hausner’s ratio, Carr’s index, bulk density, and angle of repose. Despite that, the results obtained in the traditional method lack predictability, reproducibility, sensitivity, and the actual association between the resulting data and flow behaviour. Henceforth the results varied for weight variation, content uniformity, and dissolution, etc. during the preparation of final dosage forms. To overcome these limitations of the traditional methods, the advanced techniques are being utilised to explore micro properties like the angle of internal friction, bulk density, flow function, yield loci, powder rheometry under precisely controlled conditions of consolidation stress. Ultimately these techniques help to design, choose suitable excipients, reduce time along with cost, and improve the health of society. This review focuses on some of the most commonly applied methods used in traditional and advanced shear cell testing techniques to measure the flow of powders.

Investigation of the compatibility between kaempferol and excipients by thermal, spectroscopic and chemometric methods

Compatibility is an important step in pre-formulation studies during the development of solid dosage forms. In the present study, we used thermal analysis (differential scanning calorimetry and thermogravimetry), isothermal stress testing followed by high-performance liquid chromatography and Fourier transform infrared spectroscopy complemented by two multivariate techniques (hierarchical cluster analysis and principal component analysis) to detect potential incompatibilities between kaempferol and commonly used solid dosage form excipients in binary mixtures. The excipients that were studied were starch, microcrystalline cellulose, magnesium stearate, hydroxypropylmethylcellulose, lactose, sodium lauryl sulfate and polyvinylpyrrolidone. The thermal analyses results indicated interactions occurred between kaempferol and all excipients studied except microcrystalline cellulose. However, infrared spectroscopy complemented by multivariate analysis indicated compatibility between kaempferol and all excipients. Isothermal stress testing confirmed the absence of significant change in the content of kaempferol in the binary mixtures. Our study demonstrates the importance of combining different techniques and multivariate data analysis for pre-formulation drug-excipient analysis.