Direct Compression Tablets Research Articles

Design-of-experiment approach to quantify the effect of nano-sized silica on tableting properties of microcrystalline cellulose to facilitate direct compression tableting of binary blend containing a low-dose drug

There are challenges to implementing high-speed direct compression tableting for poor flow, low-density cohesive powder. Thus, excipients with adequate flowability and bulk density are desired to facilitate this process. As a major novelty, the effect of nano-sized silica (Aerosil 200®) on the extent of flow and packing properties enhancement was evaluated. A 32 full-factorial design was applied to investigate the influence of silica load (X1; 0.5–5%) and mixing time (X2; 1–10 min) as independent variables on flow, bulk density and compaction properties of microcrystalline cellulose (MCC). Optimized MCC-silica blend was subsequently used in tableting of Albuterol Sulphate as a model low-dose drug. Regression analysis demonstrated significant (p ≤ 0.05) effect of X1 and X2 on tableting properties of MCC with pronounced effect of X1. Besides, nano-sized silica exhibited a significant improve in flowability, bulk density and compaction properties of MCC. However, at higher silica loading (over 2.75%) a reduction in flow and compaction was observed. The superior performance of MCC was achieved at silica load of (2.40%) and mixing time of (9.66 min). Moreover, the optimized blend could be directly compressed into tablets with excellent content uniformity, adequate mechanical strength, fast disintegration (63 ± 0.64 s) and dissolution (>90% after 5 min) that leads to rapid response. Ultimately, dry coating of poor flow-low density powder using nano-sized silica is a promising approach to improve the content uniformity of low-dose tablets prepared by high speed direct compression tableting.

Investigation of the Tableting Properties of Modified Dioscorea dumetorum Starch in Direct Compressed Diclofenac Tablet Formulations

Background: Modification of starch enhances their performance and improves properties such as compressibility, visco-stability, texture and dissolution. Objectives: The aim of the study was to investigate the direct compression properties of modified starch of Dioscorea dumetorum in diclofenac tablet formulations. Method: Isolated starch from Dioscorea dumetorum tubers was subject to two forms of modification and the modified products characterized with the native starch for their physicochemical and powder properties. The modified starches (5, 7.5 and 10%w/w) and microcrystalline cellulose (MCC) (10%w/w) were used in the formulation of batches of diclofenac potassium tablets via slugging and direct compression. Flowability of granules from their slugs and tablet parameters from their tablet were evaluated using standard procedures. Drug-excipient interaction studies was carried out using FTIR analysis. Results: The extracted starch was white, while the modified forms were off-white in colour. All the starches were smooth in texture and insoluble in water with swelling capacities ≤ 2.85, hydration capacities ≥ 1.22 and moisture contents ≤ 14.5%. Granules gave Carr’s indices, Hausner’s ratios and angles of repose values ranging from 10.71-18.03%, 1.12-1.22 and 20.16- 28.15°, respectively, indicating good flow. Tablet’s friability ranged from 0.01-0.04% while their hardness values was between 4.20-5.50 kp and disintegration times < 7.0 min. Dissolution profiles of the tablets showed over 70% diclofenac release within 45 min. FTIR studies showed no interaction between diclofenac and formulation excipients. Conclusion: Modified Dioscorea dumetorum starch possesses binding and disintegrating properties comparable with MCC, hence it can be used as an alternative to MCC in direct compression of tablets.

Enhancement of dissolution rate of racecadotril by liquisolid compact technology

The current investigation was used to improve the rate of dissolution of an anti-diarrheal drug i.e., racecadotril (RT) at low pH conditions (i.e., in the stomach) by reducing the water secretion and electrolyte in to the intestine by liquisolid tablets. Different formulations (liquisolid) were prepared using Avicel PH 102 as a carrier. Aerosil 200 as a coating material and sodium starch glycolate used as a disintegrant. Polyethylene glycol 200 was used as a non-volatile vehicle to dissolve the drug. FTIR, DSC, XRD and dissolution studies were conducted to characterise liquisolid tablets. Characterisation studies indicated that no interactions between carrier and drug. Solid state characterization had shown a reduction in crystallinity that further supports increment in solubility and dissolution. The optimised formulation showed a significant increase in dissolution i.e., 99.54±0.62% in 30 min compared to directly compressible tablets (38.47±0.26%). The % dissolution efficiency of racecadotril liquisolid tablets 76.86% compared to marketed tablet (27.56%) and conventional direct compression tablet (17.11%). Significant reduction in mean dissolution time of racecadotril from liquisolid tablets (6.84 min) compared to direct compression tablet (44.57 min), indicating faster release of drug and faster onset of action. Formulation of liquisolid tablets could enhance solubility, dissolution and bioavailability of racecadotril.

A Hierarchical Approach to Monitoring Control Performance and Plant-Model Mismatch

Controllers are often tuned during plant commissioning, with a fixed process model. However, over time degradation can occur in the process, the process model and the controller, making it necessary to either re-tune the controller or re-identify the process model. Authors have proposed a variety of approaches to identify plant-model mismatch (PMM) and control performance degradation (CPD). While each approach may have its own advantages and disadvantages, they are generally designed to function on different timescales. The differing timescales result in the need for a multi-level hierarchical approach to monitor, detect, and manage PMM and CPD, as illustrated through a continuous pharmaceutical manufacturing application, i.e., a direct compression tablet manufacturing process. This work also highlights the requirement for index-based metrics, that enable the impact of PMM and CPD to be quantified and assessed from a control performance monitoring perspective, to aid fault diagnosis through root cause analysis to guide maintenance decisions for continuous manufacturing applications.

Evaluating the effect of spherical crystallization of acetylsalicylic acid crystal and crystal agglomeration of Manihotesculenta starch on direct compression tablet properties

Spherical crystallization and crystal agglomeration have been used to optimize compact crystals and functional properties of powders. The aim of this work is to evaluate the effect of spherical crystallization of acetylsalicylic acid crystals and crystal agglomeration of Manihotesculenta starch on direct compression tablet. Typical spherical crystallization using three solvent system of water–ethanol-carbon tetrachloride was used to produce spherical acetylsalicylic acid. Salting-out agglomeration of gelling in water and salting in ethanol was used to produce starch-xerogel from Manihotesculenta starch. The modified products were qualified using FT-IR analysis. The analysis results showed that modification did not alter chemical nature of the products. Acetylsalicylic acid tablets were formulated using spherical-crystallizedacetylsalicylic acid with 5 and 10% w/w starch-xerogel respectively, and using acetylsalicylic acid with 5 and 10% w/w of starch, and microcrystalline cellulose respectively. The physicochemical properties of the tablets were evaluated. Astatistical 23 factorial design of the tablet properties at 5% level of significance showed that the effects of the variables are different. Theacetylsalicylic acid tablets formulated from direct compression of spherical-crystallizedacetylsalicylic acid with 5 % w/w starch-xerogel produced quality tablets comparable to standard tablets from direct compression of acetylsalicylic acid with10 % w/w microcrystalline cellulose. Spherical crystallization and crystal agglomeration optimized the compact crystals of starch and acetylsalicylic acid, and improved direct compression properties of the crystals, and drug release from tablet.

Отбелка микрокристаллической целлюлозы, полученной методом газофазного гидролиза

One of the main consumers of microcrystalline cellulose (MCC) is the pharmaceutical industry, where MCC is used as a binder and filler in direct compression of tablets. MCC is produced by acidic hydrolysis of cellulose, which usually results in a decrease in whiteness. This is due to the destruction of sugars formed during hydrolysis and the subsequent formation of colored products. The composition and properties of these products depend on the method of hydrolysis, acid concentration, temperature, and process duration. One of the most promising methods for producing MCC is gas-phase hydrolysis of cellulose with hydrogen chloride gas-air mixtures. The method has a high rate of hydrolysis, low reagent and energy consumption. The requirements of the pharmaceutical industry determine the need to produce MCC with high whiteness. The research purpose is to select bleaching modes for MCC using sodium hypochlorite and hydrogen peroxide as bleaching agents. MCC produced by gas-phase hydrolysis of bleached wood pulp was used during the study. The whiteness and intensity of the yellow tint of MCC in the bleaching process were determined by digital colorimetry on a flatbed scanner. The paper shows that sodium hypochlorite and hydrogen peroxide allow achieving the whiteness not less than 90 % and the intensity of the yellow tint not more than 3 standard units. High-quality bleaching can be carried out even for MCC samples with an initial whiteness of about 40 %. The most effective bleaching agent is sodium hypochlorite when the pH of the bleaching solution is 2–3. Hydrogen peroxide also provides high whiteness of MCC at pH of 10–11. However, the consumption of active oxygen (AO) for bleaching is more than three times higher in comparison with the consumption of active chlorine (ACh). It was found that the dyes of MCC produced by gas-phase hydrolysis consist of two chromophore groups that decolorize at different rates. The easily oxidized group of components makes up about 90 % of the total amount of dyes, and the resistant to oxidation components make up about 10 % and determine the intensity of the yellow tint of MCC. The modes of bleaching MCC with sodium hypochlorite and hydrogen peroxide to product samples with whiteness comparable to that of imported samples were determined. For citation: Sizov A.I., Pimenov S.D., Stroiteleva A.D., Stroiteleva K.D. Bleaching of Microcrystalline Cellulose Produced by Gas-Phase Hydrolysis. Lesnoy Zhurnal [Russian Forestry Journal], 2021, no. 6, pp. 173–183. DOI: 10.37482/0536-1036-2021-6-173-183

Improvement of The Photostability of Nimodipine by Using Liquisolid Compacts Technique

Liquisolid compacts are one of the modern drug formulation techniques used for drug formulation for several objectives including protection against photosensitivity. This study evaluates the photoprotective effect of the liquisolid compact technique on a calcium channel blocker antihypertensive drug, nimodipine, which is considered a photosensitive drug model. Liquisolid compact tablets of nimodipine were prepared from; Avicel PH-102 as a carrier material, (colloidal silicon dioxide, Cab-O-sil, and titanium dioxide as coating materials), croscarmellose sodium (CSS), sodium starch glycolate (SSG), crospovidone (CP) as super disintegrants, and propylene glycol as the liquid vehicle. However, the ratio of carrier to coating materials was kept constant in all formulations at 35:1. This ratio was chosen after testing the ratios 15:1, 20:1, 25:1, 30:1 and 35:1. The feasibility of the prepared liquisolid systems was also evaluated for first; the pre-compression and post-compression characteristics. Second, the possible drug-excipients interaction using FT-IR. Third, the photostability of Nimodipine in pure form, conventional tablets, and in the prepared liquisolid tablets through irradiation with a light dose of 0.55 W/m2/h visible light, 50 W/m2/h UVA and 0.27 W/m2/h UVB for 12 h in order to estimate the effect of coating material type on Nimodipine stability especially in the prepared liquisolid formulations. The results showed that all of the prepared liquisolid tablets showed satisfactory properties regarding pre and post-compression properties. Interestingly, the FTIR spectra study ruled out any interaction between nimodipine and excipients in the prepared liquisolid tablets. Besides, all of the prepared liquisolid tablets had shown a superior drug dissolution profile compared to the conventional and direct compressed tablets. Finally, 92.43% of the drug remaining was found in the liquisolid formulation (F7) after 12 h photo-irradiation as compared to 65.48% drug remaining for the pure drug substance and 75.12% for directly compressed tablets indicating that liquisolid technique had significantly inhibited the photo-degradative effect of light in the prepared liquisolid formulations. It can be concluded that the liquisolid compacts technique is a promising approach for the improvement of photostability of this photosensitive Nimodipine with an acceptable stability as well as enhanced dissolution rate.

Study of the Tableting Properties of MCR, a Newly Coprocessed Cellulose-based Direct Compression Excipient

The current need for strategies to accelerate and optimize the efforts to develop new in-expensive multifunctional direct compression tableting excipients with minimum risk to the products has urged the workers in pharmaceutical industry field to search for a simple and low cost-effective technique to tailor and engineer multi-functional excipients.

Formulation Study of a Co-Processed, Rice Starch-Based, All-in-One Excipient for Direct Compression Using the SeDeM-ODT Expert System.

A co-processed, rice starch-based excipient (CS), previously developed and shown to exhibit good pharmaceutical properties, is investigated as an all-in-one excipient for direct compression (DC). An SeDeM-ODT expert system is applied to evaluate the formulation containing CS, in comparison with those containing the physical mixture and the commercial DC excipients. The results revealed that CS showed acceptable values in all six incidence factors of the SeDeM-ODT diagram. In addition, the comprehensive indices (IGC and IGCB) were higher than 5.0, which indicated that CS could be compressed with DC technique without additional blending with a disintegrant in tablet formulation. The formulation study suggested that CS can be diluted up to 60% in the formulation to compensate for unsatisfactory properties of paracetamol. At this percentage, CS-containing tablets exhibited narrow weight variation (1.5%), low friability (0.43%), acceptable drug content (98%), and rapid disintegration (10 s). The dissolution profile of CS displayed that more than 80% of the drug content was released within 2 min. The functionality of CS was comparable to that of high functionality excipient composite (HFEC), whereas other excipients were unsuccessful in formulating the tablets. These results indicated that CS was a suitable all-in-one excipient for application in DC of tablets.

Application of the Kuenz–Leuenberger Equation as a Predictive Model of the Direct Tablet Compression Process

Application of the Kuenz–Leuenberger Equation as a Predictive Model of the Direct Tablet Compression Process

4‐in‐1 Multipurpose Excipient from Musa acuminata Fruit by Alkaline‐Steeping/Retrogradation (ASR) in Acetaminophen Tablet Formulation

AbstractThe conventional approach in the tablet formulation of acetaminophen (ACM) suggests the use of five or more different excipients in a wet granulation tableting process. The use of many excipients in tablet formulation may negatively create excipient–excipient interactions, excipient–drug interactions, exaggerated product side effects, and high drug load. Cutting‐edge technology would be the use of one excipient with a quadrupled functional purpose (4‐in‐1) by direct compression tableting. In this study, a novel two‐phase process called “alkaline‐steeping/retrogradation” (ASR) is employed to obtain the desired starch polymer excipient of quadrupled functional purpose. In phase I, the biopolymer is extracted from the unripe fruits of Musa acuminata by a modified alkaline solution steeping method, while in phase II, 50% w/w of the extracted polymer is retrograded. The retrograded product is re‐mixed with the non‐retrograded 50% w/w that is left from phase I. This gives a novel 50–50% w/w blend named Musa acuminata advanced starch polymer (MAP). To authenticate the efficiency of the ASR, the physicomechanical, analytical, and drug release properties of different concentrations of MAP/ACM solid systems are characterized to ascertain the compatibility. The ASR method produces a unique semi‐hygroscopic biopolymer excipient of quadruple‐function in ACM high‐dose tablet formulation by direct compression.

Streamlining of the Powder Mixing Process based on a Segregation Test.

In direct compression of tablets, it is crucial to maintain content uniformity within acceptable margins, especially in formulations with low drug loading. To assure it, complex and multistep mixing processes are utilized in the industry. In this study, we suggest the use of a simple segregation test to evaluate mixing process performance and mixture segregation to produce tablets having satisfying content uniformity while keeping the process as simple and low cost as possible. Eventually, the formulation propensity to segregation can be evaluated using process analytical technology (PAT) to adjust the mixing process parameters to changing source drug properties. In this study, that approach was examined on a model drug with a broad batch-to-batch variability in particle size and shape. Excipients were chosen so that the resulting blend composition mimicked some marketed formulations. For each drug batch, two formulation blends were prepared through different preparation processes (one simple and one complex) and subsequently subjected to segregation tests. From those, segregation coefficients were obtained to compare segregation tendencies and homogeneity robustness between the drug batches and the blend preparation methods. The inter-particulate interactions were substantially influenced by the drug particle morphology and size and resulted in different segregation behavior. Based on these findings, a simple segregation test proved to be a useful tool for determining the suitability of different batches of the model drug to be used in a certain formulation. Moreover, for a particular batch A, the test revealed a potential for mixing process simplification and therefore process intensification and cost reduction.

Continuous downstream processing of milled electrospun fibers to tablets monitored by near-infrared and Raman spectroscopy

Electrospinning is a technology for manufacture of nano- and micro-sized fibers, which can enhance the dissolution properties of poorly water-soluble drugs. Tableting of electrospun fibers have been demonstrated in several studies, however, continuous manufacturing of tablets have not been realized yet. This research presents the first integrated continuous processing of milled drug-loaded electrospun materials to tablet form supplemented by process analytical tools for monitoring the active pharmaceutical ingredient (API) content. Electrospun fibers of an amorphous solid dispersion (ASD) of itraconazole and poly(vinylpyrrolidone-co-vinyl acetate) were produced using high speed electrospinning and afterwards milled. The milled fibers with an average fiber diameter of 1.6 ± 0.9 µm were continuously fed with a vibratory feeder into a twin-screw blender, which was integrated with a tableting machine to prepare tablets with ~ 10 kN compression force. The blend of fibers and excipients leaving the continuous blender was characterized with a bulk density of 0.43 g/cm3 and proved to be suitable for direct tablet compression. The ASD content, and thus the API content was determined in-line before tableting and at-line after tableting using near-infrared and Raman spectroscopy. The prepared tablets fulfilled the USP <905> content uniformity requirement based on the API content of ten randomly selected tablets. This work highlights that combining the advantages of electrospinning (e.g. less solvent, fast and gentle drying, low energy consumption, and amorphous products with high specific surface area) and the continuous technologies opens a new and effective way in the field of manufacturing of the poorly water-soluble APIs.

Direct compression tablet formulation of celecoxib enabled with a pharmaceutical solvate

Celecoxib, an anti-inflammatory drug for pain and arthritis, is currently only available in capsule form. To reduce the onset time for a faster action and to lower the manufacturing cost, the tablet dosage form is more preferred. However, the commercial celecoxib (Form III) is not suitable for direct compression (DC) tablet manufacture due to poor flow, low bulk density, and tablet lamination. In this work, we overcome these challenges using a pharmaceutically acceptable dimethyl sulfoxide (DMSO) solvate of celecoxib. Aided with the DMSO solvate, an acceptable DC tablet formulation was successfully developed to manufacture tablets containing 200 mg celecoxib, with satisfactory manufacturability, disintegration, and in vitro dissolution performance.

Application of Aquasolv Lignin in ibuprofen-loaded pharmaceutical formulations obtained via direct compression and wet granulation

AS (Aquasolv) Lignin produced via Liquid Hot Water Pretreatment and Enzymatic Hydrolysis has shown potential as an active pharmaceutical ingredient and/or excipient in solid dosage forms. Moreover, lignin is safe to consume and presents antioxidant and antidiabetic capacity, properties that can add to solid dosage forms in pharmaceuticals. This work aimed to evaluate the performance of tablets produced via direct compression and wet granulation when lignin is used in combination with commercial excipients. In order to find optimal tablet performance, different lignin formulations were assessed, and the concentrations were given by extreme vertices mixture design (13 formulations). The blends were composed of AS Lignin, Microcrystalline Cellulose, and Lactose monohydrate and the optimized blend was found to be 14.53 w/w% of disintegrant, 26.57 w/w% of binder and 58.9 w/w% of AS lignin. This proportion was further used to evaluate the performance of lignin-based tablets in drug release, using Ibuprofen as a drug model (50 w/w% and 70 w/w%) and for comparison of direct compression with wet granulation. Direct compressed tablets resulted in higher drug dissolution rates when compared with wet granulation, nevertheless; both tableting techniques showed promising results for lignin. More than 5 formulations tested in this work are compliant with International Pharmacopoeia regulations for solid dosage pharmaceutical forms, thus AS Lignin shows potential to be used as an excipient in pharmaceutical formulations. Industrial relevanceIndustrially, AS Lignin appears as promising excipient in the pharmaceutical technologies as well as boost in the biorefining technologies in the following years. Lignin produced is free of sulfur, can be labelled as clean and environmentally-friendly and in this study, was proven this non-cytotoxic AS lignin can be used for excipients and drug carriers. The findings in this paper showed the use of product formulation for life science purposes, thus stressing one of possibilities for lignin valorization in biorefineries.

Directly Compressed Tablets: A Novel Drug‐Containing Reservoir Combined with Hydrogel‐Forming Microneedle Arrays for Transdermal Drug Delivery

Microneedle (MN) patches consist of a hydrogel-forming MN array and a drug-containing reservoir. Drug-containing reservoirs documented in the literature include polymeric films and lyophilized wafers. While effective, both reservoir formulations are aqueous based, and so degradation can occur during formulation and drying for drugs inherently unstable in aqueous media. The preparation and characterization of novel, nonaqueous-based, directly compressed tablets (DCTs) for use in combination with hydrogel-forming MN arrays are described for the first time. In this work, a range of drug molecules are investigated. Precipitation of amoxicillin (AMX) and primaquine (PQ) in conventional hydrogel-forming MN arrays leads to use of poly(vinyl alcohol)-based MN arrays. Following in vitro permeation studies, in vivo pharmacokinetic studies are conducted in rats with MN patches containing AMX, levodopa/carbidopa (LD/CD), and levofloxacin (LVX). Therapeutically relevant concentrations of AMX (≥2µg mL-1 ), LD (≥0.5µg mL-1 ), and LVX (≥0.2µg mL-1 ) are successfully achieved at 1, 2, and 1 h, respectively. Thus, the use of DCTs offers promise to expand the range of drug molecules that can be delivered transdermally using MN patches.

Development of piroxicam mini-tablets enabled by spherical cocrystallization.

We examined the potential of the spherical cocrystallization (SCC) technology in simultaneously enhancing tablet manufacturability and dissolution of poorly soluble drugs by developing a mini-tablet formulation of piroxicam. The manufacturing of mini-tablets using a direct compression (DC) process is more challenging than conventional tablets because of the much stricter requirement on the micromeritic properties of formulated powders. The SCC process in this work involved two steps: 1) preparing a new piroxicam-ferulic acid (PRX-FA) cocrystal, and 2) forming spherical agglomerates with the aid of a suitable bridging liquid. The PRX-FA cocrystal exhibited enhanced solubility as well as improved plasticity. The bridging liquid, a mixture of chloroform and ethyl acetate (EA) (1: 2, v/v), was chosen based on the high computed adsorption energy of chloroform and EA on morphologically dominating crystal faces of PRX-FA. The improved flowability, tabletability, and dissolution rate of spherical PRX-FA enabled the successful development of a DC mini-tablet formulation with a high PRX loading (41wt%). This example shows that SCC is a powerful enabling technology for DC tablet formulation development of challenging drugs.

Fine grade engineered microcrystalline cellulose excipients for direct compaction: Assessing suitability of different dry coating processes

Recent work showed that contrary to conventional wisdom, fine surface engineered excipients outperform their larger counterparts in blends of highly loaded blends of cohesive drug powders in terms of their packing, flowability and tablet tensile strength. Here, two continuous devices, fluid-energy mill (FEM) and conical mill (Comil), are compared with LabRAM, a batch device used in previous work, for nano-silica dry coating of microcrystalline cellulose (MCC) excipients, 20 and 30 μm. Coated MCCs from all three devices had higher bulk densities and flow function coefficients (FFCs) compared with Avicel PH-102. Silica coating quality was best with LabRAM, but also good with FEM and Comil, although Comil was less effective for the finer MCC. However, the better coating quality of LabRAM had a downside of having poorer compaction properties. The most surprising outcome was that multi-component blends of 17 wt% coated MCC with 60 wt % Ibuprofen 50 had higher bulk density, higher or similar flowability, higher tablet tensile strength, and comparable Ibuprofen dissolution from tablets, compared to those with Prosolv 50, a silicified excipient. The FEM dry coated MCC blends, having only 0.17 wt% silica, performed the best, having desirable bulk density, FFC, and tensile strength that could facilitate high-speed direct compression tableting. In summary, considering that achieving best coating quality need not be the primary objective, FEM may be the best option for producing desired sized dry coated fine excipients.

End-to-end continuous manufacturing of conventional compressed tablets: From flow synthesis to tableting through integrated crystallization and filtration.

An end-to-end continuous pharmaceutical manufacturing process was developed for the production of conventional direct compressed tablets on a proof-of-concept level for the first time. The output reaction mixture of the flow synthesis of acetylsalicylic acid was crystallized continuously in a mixed suspension mixed product removal crystallizer. The crystallizer was directly connected to a continuous filtration carousel device, thus the crystallization, filtration and drying of acetylsalicylic acid (ASA) was carried out in an integrated 2-step process. Steady state was reached during longer operations and the interaction of process parameters was evaluated in a series of experiments. The filtered crystals were ready for further processing in a following continuous blending and tableting experiment due to the good flowability of the material. The ASA collected during the crystallization-filtration experiments was fed into a continuous twin-screw blender along with microcrystalline cellulose as tableting excipient. After continuous blending Near-Infrared spectroscopy was applied to in-line analyze the drug content of the powder mixture. A belt conveyor carried the mixture towards an eccentric lab-scale tablet press, which continuously produced 500mg ASA-loaded compressed tablets of 100mg dose strength. Thus, starting from raw materials, the final drug product was obtained by continuous manufacturing steps with appropriate quality.

On-Demand Manufacturing of Direct Compressible Tablets: Can Formulation Be Simplified?

Oral direct compressible tablets are the most frequently used drug products. Manufacturing of tablets requires design and development of formulations, which need a number of excipients. The choice of excipients depends on the concentration, manufacturability, stability, and bioavailability of the active pharmaceutical ingredients (APIs). At MIT, we developed a miniature platform for on-demand manufacturing of direct compressible tablets. This study investigated how formulations could be simplified to use a small number of excipients for a number of different API's in which long term stability is not required. Direct compressible tablets of five pharmaceutical drugs, Diazepam, Diphenhydramine HCl, Doxycycline Monohydrate, Ibuprofen, and Ciprofloxacin HCl, with different drug loadings, were made using direct compression in an automated small scale system.. The critical quality attributes (CQA) of the tablets were assessed for the quality standards set by the United States Pharmacopeia (USP). This miniature system can manufacture tablets - on-demand from crystalline API using the minimum number of excipients required for drug product performance. All drug tablets met USP quality standards after manufacturing and after 2weeks of accelerated stability test, except for slightly lower drug release for Ibuprofen. On-demand tablets manufacturing where there is no need for long term stability using a flexible, miniature, automated (integrated) system will simplify pharmaceutical formulation design compared to traditional formulations. This advancement will offer substantial economic benefits by decreasing product time-to-market and enhancing quality.