Lubricants in Pharmaceutical Solid Dosage Forms (2025)

Acetylation and Evaluation of Taro Boloso-I Starch as Directly Compressible Excipient in Tablet Formulation

Advances in Pharmacological and Pharmaceutical Sciences, 2020

Taro Boloso-I (TB1), a newly improved Colocasia esculenta variety, is a potential source of starch with high yield. However, to improve some limitations of the native starches (NS), such as flowability and compactibility, different physical and chemical starch modifications have been employed. Acetylation is one of the chemical modifications which improves the flow and compaction of the NS, which are prerequisite during direct compression (DC) of tablets. Hence, in this study, TB1 starch was acetylated using acetic anhydride and evaluated as an ideal excipient for direct compression. Starch acetates (SA) with a degree of substitution (DS) of 0.072 (SA1) and 0.695 (SA2) were produced and evaluated. FTIR spectra of the SAs were used to verify the acetylation of the NS. Powder flow evaluation parameters showed significant improvement in the flow properties of the NS following acetylation. In addition, the swelling power, solubility, and compactibility were also improved. Tensile strength (TS) of the tablets comprising SAs only, SA1 (41.40) and SA2 (63.43 Kg/cm2), was significantly higher than tablets made of the NS (31.96) and Starch 1500® (15.12 Kg/cm2). The SAs also showed lower sensitivity towards lubrication than the NS and Starch 1500® as lower lubricant sensitivity ratios were recorded. In addition, tablets comprising the SAs satisfactorily accommodated at least up to 50 % w/w paracetamol—compared to 30 % w/w by Starch 1500®—upon DC processing. The paracetamol tablets comprising SAs also complied with the United States Pharmacopeia specifications for disintegration and dissolution studies. Therefore, taking all the facts into consideration, the SAs could be potential DC excipients in tablet formulations.

Additive Manufacturing of Oral Tablets: Technologies, Materials and Printed Tablets

2021

Additive manufacturing (AM), also known as three-dimensional (3D) printing, enables fabrication of custom-designed and personalized 3D constructs with high complexity in shape and composition. AM has a strong potential to fabricate oral tablets with enhanced customization and complexity as compared to tablets manufactured using conventional approaches. Despite these advantages, AM has not yet become the mainstream manufacturing approach for fabrication of oral solid dosage forms mainly due to limitations of AM technologies and lack of diverse printable drug formulations. In this review, AM of oral tablets are summarized with respect to AM technology. A detailed review of AM methods and materials used for the AM of oral tablets is presented. This article also reviews the challenges in AM of pharmaceutical formulations and potential strategies to overcome these challenges.

Formulation of sublingual promethazine hydrochloride tablets for rapid relief of motion sickness

Saudi Pharmaceutical Journal, 2021

The delivery of antihistaminic agents via the oral route is problematic, especially for elderly patients. This study aimed to develop a sublingual formulation of promethazine hydrochloride by direct compression, and to mask its intensely bitter taste. Promethazine hydrochloride (PMZ) sublingual tablets prepared by direct compression were optimized using Box-Behnken full factorial design. The effect of a taste-masking agent (Eudragit E 100, X1), superdisintegrant (crospovidone; CPV, X2) and lubricant (sodium stearyl fumarate; SSF, X3) on sublingual tablets' attributes (responses, Y) was optimized. The prepared sublingual tablets were characterized for hardness (Y1), disintegration time (Y2), initial dissolution rate (IDR; Y3) and dissolution efficiency after 30 min (Dissolution Efficiency (DE); Y4). The obtained results showed a significant positive effect of the three independent factors on tablet hardness (P < 0.05), and the interactive effect of Eudragit E 100 and CPV on tablet hardness was significant. Disintegration time was mainly affected by Eudragit E 100 and CPV concentrations. Moreover, IDR was employed to assess the taste masking effect, lower values were obtained at higher Eudragit E 100 concentration despite it was statistically insignificant (p > 0.05). Optimized formulation that was suggested by the software was composed of: Eudragit E 100 (X1) = 2.5% w/w, CPV (X2) = 4.13% w/w, and SSF (X3) = 1.0% w/w. The observed values of the optimized formula were found to be close to the predicted optimized values. The Differential Scanning Calorimetric (DSC) studies indicated no interaction between PMZ and tablet excipients.

Production of Reproducible Filament Batches for the Fabrication of 3D Printed Oral Forms

Pharmaceutics

Patients need medications at a dosage suited to their physiological characteristics. Three-dimensional printing (3DP) technology by fused-filament fabrication (FFF) is a solution for manufacturing medication on demand. The aim of this work was to identify important parameters for the production of reproducible filament batches used by 3DP for oral formulations. Amiodarone hydrochloride, an antiarrhythmic and insoluble drug, was chosen as a model drug because of dosage adaptation need in children. Polyethylene oxide (PEO) filaments containing amiodarone hydrochloride were produced by hot-melt extrusion (HME). Different formulation storage conditions were investigated. For all formulations, the physical form of the drug following HME and fused-deposition modeling (FDM) 3D-printing processes were assessed using thermal analysis and X-ray powder diffraction (XRPD). Filament mechanical properties, linear mass density and surface roughness, were investigated by, respectively, 3-point bend...

Effect of Contamination on the Friction and Wear of Carboxylic Acids in Aqueous Lubricants

Tribology Letters, 2018

The friction and wear mechanisms of water-based fluids consisting of various types of carboxylic acids have been systematically investigated using a ball-on-disc tribometer on a super duplex stainless steel under boundary lubricating conditions. Under water-based lubrication a decrease in friction was found for each of the tested carboxylic acids with a hydrocarbon chain longer than 12 carbon atoms. However, wear reduction was only seen for the carboxylic acids with a hydrocarbon chain longer than 16 carbon atoms and when the concentration of the shorter carboxylic acids increased above a critical value. In addition, it was found that when the lubricant is contaminated with bivalent metal ions like Ca 2+ or Mg 2+ , the frictional performance becomes worse however, wear improved. Indeed, by increasing the concentration of bivalent alkaline metal ions, the adsorption ability of carboxylic acids to the steel surface decreased leading to higher friction and the presence of Na + ions facilitated the wear improvement. This is explained by the formation of polyelectrolyte complexes between the metal ions dissolved in the lubricant and the carboxylic acid molecules. To compensate for the detrimental effects in friction, a chelating strategy has been implemented and explained in detail.

Impacts of Lubricant Type on the Densification Behavior and Final Powder Compact Properties of Cu–Fe Alloy under Different Compaction Pressures

Materials

A Cu–15Fe alloy was fabricated using a powder metallurgy (PM) route, with the addition of different solid lubricants (i.e., paraffin wax (PW) and stearic acid (SA) as well as their composites (PW+SA)). Green compacts were produced via cold compaction at different pressure levels of 50 MPa, 200 MPa, and 350 MPa, then sintered for 60 min under vacuum at 1050 °C. The systematic evolution of the densification, porosity, and pore-size behavior were studied. Vickers Hardness Tests were used to measure hardness. The analysis of the morphological alterations was performed using scanning electron microscopy (SEM) and X-ray diffraction (XRD) techniques. Moreover, under dry sliding conditions, pin-on-disk wear tests were conducted in order to determine tribological properties such as the coefficient of friction (µ), specific wear rate (K), and friction temperature gain. Results revealed that the lubrication process and compaction pressure play a crucial role in defining the characteristics of ...

Controlling reactivity through liquid assisted grinding: the curious case of mechanochemical fluorination

Green Chemistry, 2017

We have identified an example of a mechanochemically milled organic reaction where liquid-assisted grinding controls the selectivity, such a phenomenon has not been reported/observed before.

The Milky Way: paediatric milk-based dispersible tablets prepared by direct compression - a proof-of-concept study

The Journal of pharmacy and pharmacology, 2016

Dispersible tablets are proposed by the World Health Organization as the preferred paediatric formulation. It was hypothesised that tablets made from a powdered milk-base that disperse in water to form suspensions resembling milk might be a useful platform to improve acceptability in children. Milk-based dispersible tablets containing various types of powdered milk and infant formulae were formulated. The influence of milk type and content on placebo tablet properties was investigated using a design-of-experiments approach. Responses measured included friability, crushing strength and disintegration time. Additionally, the influence of compression force on the tablet properties of a model formulation was studied by compaction simulation. Disintegration times increased as milk content increased. Compaction simulation studies showed that compression force influenced disintegration time. These results suggest that the milk content, rather than type, and compression force were the most ...

Pharmaceutical development of tablets containing a spray-dried optimized extract from Lippia origanoides H. B. K.: influence of excipients and toxicological assessment

Brazilian Journal of Pharmaceutical Sciences, 2018

Lippia origanoides is a honey shrub which has showed hypotensive potential assessed by in vivo studies. The aim of this work is the development of a pharmaceutical formulation composed by an optimized extract obtained from aerial parts of L. origanoides. The quantification of the naringenin marker in the dry extract and tablets developed was performed, as well as the assessment of the oral acute toxicity in rats. The hydroalcoholic extract of L. origanoides was spray-dried with the addition of colloidal silicon dioxide (Lo-HAE/CSD), and then applied in the preparation of eight different lots of tablets. The influence of the diluent (cellulose or babassu mesocarp), the presence of binder, and the percentage of lubricant, as well as organoleptic and physicochemical characteristics were screened. For the quantification of the marker content both in Lo-HAE/CSD and in the tablets, an analytical curve of the naringenin standard was fitted, and the samples were then analyzed in UFLC. The toxicological assessment was performed in female Wistar rats according to the Acute Toxic Class Method from OECD. The developed tablets produced meet acceptable macroscopic characteristics, and the presence of babassu as diluent provided improved physicochemical properties. The best content of Lo-HAE/CSD in the tablet (100.27%) was identified for the lot containing babassu, composed by 1.0% magnesium stearate, without PVP binder in its formulation. Moreover, Lo-HAE/CSD showed no signs of toxicity. Therefore, the babassu mesocarp powder is a promising pharmaceutical excipient for the development of herbal tablets containing the Lippia origanoides extract.

Evaluation of Microwave-Assisted Extraction Method for Preparation and Assessment of Thai Herbal Medicine Oral Tablets With Enriched Phytochemical Compounds

AAPS PharmSciTech, 2021

In developing countries, populations have employed herbal medicines for primary health care because they are believed to be more appropriate to the human body and have less side effects than chemically synthesized drugs. The present study aimed to develop and evaluate herbal tablets incorporated with a Thai traditional medicinal extract, U-pa-ri-waat (URW), using microwave-assisted extraction (MAE). The extraction efficiency for URW using MAE and traditional solvent extraction was compared based on the percent yield after spray drying. URW tablets were prepared using the dry granulation method. The optimized products were assessed using standard characterization methods based on the United States and British Pharmacopeias. DPPH and ABTS radical scavenging assays were performed to analyze the antioxidant capacity of the microwave-assisted extracts. The results revealed that the flowability of the dry granule with added maltodextrin was improved compared to a granule without additives, as indicated by an angle of repose of 33.69 ± 2.0°, a compressibility index of 15.38 ± 0.66, and a Hausner's ratio of 1.18 ± 0.06. The resulting formulation produced flat tablets with uniform weight variation, hardness, thickness, friability, and optimum disintegration time. The URW extracts showed antioxidant activity and MAE with maltodextrin carrier displayed the strongest DPPH and ABTS radical activities with IC50 values of 1.60 ± 0.02 μg/mL and 4.02 ± 0.24 μg/mL, respectively. The URW tablet formulation passed the quality control tests. Storage of the formulation tablets for 90 days under accelerated conditions had minimal effects on tablet characteristics.

Lubrication empirical model to predict tensile strength of directly compressed powder blends

International Journal of Pharmaceutics, 2021

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Thermo-Analytical and Compatibility Study with Mechanistic Explanation of Degradation Kinetics of Ambroxol Hydrochloride Tablets under Non-Isothermal Conditions

Pharmaceutics, 2021

Ambroxol hydrochloride (AMB), used as a broncho secretolytic and an expectorant drug, is a semi-synthetic derivative of vasicine obtained from the Indian shrub Adhatoda vasica. It is a metabolic product of bromhexine. The paper provides comprehensive and detailed research on ambroxol hydrochloride, gives information on thermal stability, the mechanism of AMB degradation, and data of practical interest for optimization of formulation that contains AMB as an active compound. Investigation on pure AMB and in commercial formulation Flavamed® tablet (FT), which contains AMB as an active compound, was performed systematically using thermal and spectroscopic methods, along with a sophisticated and practical statistical approach. AMB proved to be a heat-stable and humidity-sensitive drug. For its successful formulation, special attention should be addressed to excipients since it was found that polyvinyl pyrrolidone and Mg stearate affect the thermal stability of AMB. At the same time, lact...

DSC, FT-IR, NIR, NIR-PCA and NIR-ANOVA for determination of chemical stability of diuretic drugs: impact of excipients

Open Chemistry, 2018

It is well known that drugs can directly react with excipients. In addition, excipients can be a source of impurities that either directly react with drugs or catalyze their degradation. Thus, binary mixtures of three diuretics, torasemide, furosemide and amiloride with different excipients, i.e. citric acid anhydrous, povidone K25 (PVP), magnesium stearate (Mg stearate), lactose, D-mannitol, glycine, calcium hydrogen phosphate anhydrous (CaHPO4) and starch, were examined to detect interactions. High temperature and humidity or UV/VIS irradiation were applied as stressing conditions. Differential scanning calorimetry (DSC), FT-IR and NIR were used to adequately collect information. In addition, chemometric assessments of NIR signals with principal component analysis (PCA) and ANOVA were applied. Between the excipients examined, lactose and starch did not show any interactions while citric acid, PVP, Mg stearate and glycine were peculiarly operative. Some of these interactions were s...

Fabrication of Direct Compressible Tablets Containing Chatuphalathika Extract Obtained through Microwave-Assisted Extraction: An Optimization Approach

Scientia Pharmaceutica

This research sought to optimize the microwave-assisted extraction of Chatuphalathika as an herbal recipe maximizing the active compounds and the antioxidant activity by the Box–Behnken design. Three factors—microwave power, time, and cycle—were varied. Eight responses—extraction yield, total phenolic content, gallic acid content, corilagin content, chebulagic acid, chebulinic acid, IC50 from DPPH assay, and IC50 from FRAP assay—were monitored. Furthermore, cytotoxicity was evaluated to ensure the safety of the extract. After that, the optimized extract was compressed into tablets. The results showed that the optimal condition of the microwave-assisted extraction gave the simultaneous maximum extraction yield, total phenolic content, and antioxidant activity with a microwave power of 450 W for 30 s and 3 cycles. The extract obtained from the optimal condition exhibited a good safety profile although a concentration of 5 mg/mL was used. The optimized tablets were achieved when a comp...

Compatibility study of hydroxychloroquine sulfate with pharmaceutical excipients using thermal and nonthermal techniques for the development of hard capsules

Journal of Thermal Analysis and Calorimetry, 2019

Hydroxychloroquine is effectively used in the treatment for malaria, lupus erythematosus and rheumatoid arthritis. The study of drug-excipient compatibility is an important tool for the development of safe and effective pharmaceutical forms. The present study describes the use of thermal and nonthermal techniques for evaluating the physicochemical compatibility of hydroxychloroquine with excipients for the development of solid dosage forms, including microcrystalline cellulose, corn starch, mannitol, magnesium stearate and colloidal silicon dioxide. The analytical techniques employed to evaluate the drug and the drug-excipient interactions in solid binary mixtures (1:1 w:w) were differential scanning calorimetry (DSC), thermogravimetry, Fourier transform infrared spectroscopy (FTIR) and isothermal stress test. Four different formulations were prepared and drug dissolution test was determined by rotating-basket system method in water. Evidence of solid-state interactions of hydroxychloroquine and mannitol, magnesium stearate and colloidal silicon dioxide was observed in the DSC analysis and subsequently confirmed by FTIR; however, no degradation profile was observed by HPLC and no interference was seen in the drug dissolution rate and no change in physicochemical properties of hydroxychloroquine was observed. The combination of techniques is very important to correctly identify drug-excipients incompatibilities in the earliest stage of a formulation design in order to ensure the choice of suitable excipients for the development of stable and effective dosage forms of hydroxychloroquine.