A Novel Alginate Film Based on Nanocoating Approach for Enteric-Release Tablets.

The objective of this study was to propose a new coating film for biodegradable polymers and environmentally friendly processing. Here, a novel implementation of solid lipid nanoparticles (SLN) into a biodegradable alginate (ALG) film composition created a new gastric-resistant film for an enteric-release tablet. Experiments were performed on a water-soluble substance (thiamine nitrate) to characterize the effects of SLN upon the addition of the ALG coating formulation. The coated tablets or cast films were characterized based on delayed-release properties, surface morphology, moisture resistance, and chemical interactions. The SLN-ALG film displayed gastric-resistant properties (< 10% drug substance dissolved at pH 1.2) and rapid disintegration in the intestinal medium (pH 6.8). Morphological analysis using a microscope and scanning electron microscope confirmed the uniformity and smoothness of the SLN-ALG film, which improved the mechanical properties of the film. Fourier transform infrared spectroscopy and differential scanning calorimetry indicated that SLN contributed to the formation of the film, which maintained free carboxylic groups, making the SLN-ALG film a higher acid resistance, but soluble in pH 6.8 buffer. These promising results suggest a novel nanotechnology-based coating formulation for various enteric-release dosage forms. Because of their biodegradability, the proposed ingredients and processes are safe and environment-friendly.

Towards a Better Understanding of the Post-Gastric Behavior of Enteric-Coated Formulations.

PURPOSE: The aim of our work was to develop a biorelevant dissolution method for a better understanding of the in vivo performance of delayed-release tablet formulations. METHODS: The typical pH profile and residence times in the stomach and small intestine were determined in fasted conditions based on the published results of swallowable monitoring devices. Then, a multi-stage pH shift dissolution method was developed by adding different amounts of phosphate-based buffer solutions to the initial hydrochloric acid solution. Because of the highly variable in vivo residence times in the stomach, two alternatives of the method were applied, modeling rapid and slow gastric emptying as well. This approach provided an opportunity to study the effect of the acidic treatment on post gastric release. Six enteric-coated low-dose acetylsalicylic acid (ASA) formulations including the reference Aspirin Protect were tested as a model compound. Moreover, the thickness of the coating of each formulation was investigated by scanning electron microscope. RESULTS: Comparing the in vitro results to the known properties of the formulations, the new method was found to be more discriminative than the USP dissolution method. Ingredients affecting the in vitro dissolution, and thus probably the in vivo performance, were identified in both the tablet core and the coating of the tested formulations. The limited available in vivo data also indicated an increased predictivity. CONCLUSION: Overall, the presented method may be an efficient tool to support the development of enteric coated generic formulations.

Alternatives to titanium dioxide in tablet coating.

Titanium dioxide (TiO2) is one of the most commonly used pharmaceutical excipients. It is widely used as a white pigment in tablet and pellet coatings. However, it has recently been under massive criticism as a number of studies suggest a cancerogenic potential. It can therefore no longer be taken for granted that TiO2 will continue to be universally available for drug products. Finding suitable alternatives is hence of special relevance. In this study, a number of different pigments were coated on tablets and their covering potential analyzed. None of the alternative pigments showed comparable effectiveness and efficiency to TiO2, though the CaCO3/CaHPO4-based coating showed the second-best results. Regarding the ability to protect photosensitive active ingredients, ZnO showed a comparable potential as TiO2, while all other pigments failed. Using the alternative pigments as markers for in-line Raman spectroscopy as a process analytical technology was challenging and led to increased prediction errors. Again, the CaCO3/CaHPO4-based coating was the only of the tested alternatives with satisfying results, while all other pigments led to unacceptably high prediction errors.

Coating characterization by hyperspectroscopy and predictive dissolution models of tablets coated with blends of cellulose acetate and cellulose acetate phthalate.

The objective of current research was to develop the models of dissolution prediction of tablets coated with cellulose acetate (CA 320S or CA 398-10) and cellulose acetate phthalate (C-A-P) blends. Independent variables selected were coating percent (X1) and percent of CA 320S or CA 398-10 (X2) in the blend. Dependent variables selected were dissolution in 1 (Y1), 8 (Y2), and 24 h (Y3). Diclofenac sodium core tablets were coated with blend of either CA 320S and C-A-P or CA 398-10 and C-A-P at approximately 5, 7.5, and 10% weight gain. CA 320S and CA 398-10 content in the corresponding blends varied from 33.3-66.7% and 25.0-50.0% relative to C-A-P, respectively. Dissolution was performed in phosphate buffer 6.8 using USP apparatus 2. Coated tablets were also characterized for surface morphology and coating uniformity by near infrared hyperspectroscopy. Y1, Y2, and Y3 were statistically (p < 0.05) affected by X2 in CA 320S/C-A-P and CA 398-10/C-A-P blends coated tablets. On the other hand, X1 had statistically significant (p < 0.05) effect only on the Y3 in CA 320S/C-A-P while Y1 was statistically (p < 0.05) affected by X2 in CA 398-10/C-A-P. Analysis of variance also indicated statistically significant (p < 0.05) effect of the studied variables on the dependent variables for both the blends. The models were verified by independent experiment. Model predicted and empirical values of Y1, Y2, and Y3 were close with maximum residual of 7.0%. In conclusion, dissolution can be modulated by varying composition of blend, polymer type, and coating weight.

Modified-release oral pellets for duodenum delivery of doxycycline hyclate.

To minimize the gastric and esophageal injury effect, a system to deliver doxycycline hyclate (DOXY) to the duodenum area is needed. DOXY-containing modified-release oral pellets (DMOP) coated with hydroxypropyl methylcellulose phthalate HP-55 (HPMCP HP-55) and hydroxypropyl methylcellulose E15 (HPMC E15) appear to be a reasonable choice. This coating layer dissolves at pH 5.5, which is the pH of the duodenum, but not at a gastric pH (1.2). The formulation and preparation of DMOP were optimized, and a scale-up test was performed. The results showed that the production reproducibility was acceptable, and the quality of DMOP well met the standards of Chinese Pharmacopeia (Ch.P, 2015 edition). Notably, the accumulated DOXY release was lower than 50% at pH 1.2 (20 min) and higher than 85% at pH 5.5, which met the USP40-NF35 standard for DOXY modified-release formulations. Moreover, the storage stability of DMOP with different packages was investigated by stress testing, accelerated and long-term testings. The stability of DMOP was maintained up to 12 months, in terms of DOXY content and in vitro release behavior. The results seem to suggest that DMOP could be a promising duodenum delivery system.

Comparison of the coating process and in vitro dissolution of 3 mm gastro-resistant minitablets and 5 mm gastro-resistant tablets with pantoprazole.

Minitablets are solid oral forms, which, due to their size (1-3 mm), may be easily swallowed by children. The administration of minitablets in a certain number of units allows for flexible dosing for a broad age group of paediatric patients, which is particularly important for modified-release drugs. In this study, enteric-coated minitablets (3 mm) with pantoprazole were developed and compared to conventional tablets (5 mm). Eudragit L 30D 55® and Acryl Eze II® films, which were 50 and 80 µm thick, respectively, were applied using two different fluid bed systems. The increase in the pantoprazole release rate occurred not only due to the application of a thinner film but also due to the reduction in the size of the core independent of the coating apparatus that was used. In contrast to minitablets, the thin film's thickness was insufficient for 5 mm tablets and a loss of gastro-resistance was observed. The insertion of minitablets into a hard gelatine capsule did not affect drug release from the minitablets under in vitro conditions.

A Thermodynamic Balance Model for Liquid Film Drying Kinetics of a Tablet Film Coating and Drying Process.

A tablet film coating and drying process was assessed by an experimentally validated thermodynamic balance model. Mass conservation equations were derived for the process air and the aqueous coating solution. Thermodynamic behavior of the solution was described by evaporation at the tablet surface and penetration into the tablet. Energy balance equations including heat loss to the atmosphere were coupled to the mass conservation equation. Experimental data using the ConsiGma™ coater (GEA, Belgium) were used for both parameter estimation and model validation. The results showed the proposed model can investigate primitive outlet variables and further internal variables representing evaporation and penetration. A sensitivity analysis revealed that evaporation depended more on the input parameters while penetration hinges on the tablet properties, particularly on the tablet volume affecting the tablet porosity.

New Perspective Enteric-Coated Tablet Dosage Form for Oral Administration of Ceftriaxone: In Vitro and In Vivo Assessments.

Ceftriaxone (CTX) is a widely used injectable third-generation cephalosporin that exhibits broad-spectrum antibacterial activity. Unfortunately, the oral route of this drug suffers different encumbrances, such as instability in the upper part of the GIT and enzymatic degradation, as well as poor permeability. There is no reported tablet dosage form for this drug. In this respect, the authors investigated the possibility of developing an enteric-coated oral tablet of CTX that would be helpful for better patient compliance. The tablet consists of directly compressed core of CTX, citric acid (CA), sodium chloride (NaCl), and two biopolymers-chitosan (CH), a permeation enhancer, and silicified microcrystalline cellulose (SMCC), a wicking agent. Both biopolymers are naturally occurring polysaccharides that are biodegradable in the colon and able to incorporate acid labile drugs. CA is a pH modulator to protect CTX from protease enzymes, while NaCl is a translocation enhancer that helps drug penetration. The enteric coat of the core was shellac (SH) with plasticizer glycerol tristearate (GTS) and CA that was applied by direct compression (dry coating). The solventless heat curable coat resulted in an enteric-coated tablet that complies with the USP pharmacopeia. The optimized formula was further subjected to in vitro release and stability studies, as well as ingredient compatibility. In vivo oral bioavailability of the enteric-coated tablets in rabbits gave promising results (absolute bioavailability of about 80%). Synergistically, all ingredients together augmented oral bioavailability of CTX. This developed formula could be a perspective delivery system for those drugs intended to be absorbed from the colon such as peptides and peptide-like drugs.

Unpredictable Performance of pH-Dependent Coatings Accentuates the Need for Improved Predictive in Vitro Test Systems.

First introduced in the second half of the 19th century, enteric coatings are commonly used to protect acid-labile drugs, reduce the risk of gastric side effects due to irritating drugs, or for local drug delivery to the lower gastrointestinal (GI) tract. The currently available enteric-coatings are based on pH-sensitive weakly acidic polymers. Despite the long history of their use, the causes behind their performance often being unpredictable have not been properly investigated with most of the attention being focused only on the gastric emptying. However, little attention has been given to the postgastric emptying disintegration and dissolution of these dosage forms. This lack of attention has contributed to the difficulty in predicting the in vivo behavior of these dosage forms and to cases of bioavailability problems with some enteric-coated products. Therefore, increased attention needs to be given to this issue.

New film-coated tablet formulation of deferasirox is well tolerated in patients with thalassemia or lower-risk MDS: Results of the randomized, phase II ECLIPSE study.

Once-daily deferasirox dispersible tablets (DT) have a well-defined safety and efficacy profile and, compared with parenteral deferoxamine, provide greater patient adherence, satisfaction, and quality of life. However, barriers still exist to optimal adherence, including gastrointestinal tolerability and palatability, leading to development of a new film-coated tablet (FCT) formulation that can be swallowed with a light meal, without the need to disperse into a suspension prior to consumption. The randomized, open-label, phase II ECLIPSE study evaluated the safety of deferasirox DT and FCT formulations over 24 weeks in chelation-naïve or pre-treated patients aged ≥10 years, with transfusion-dependent thalassemia or IPSS-R very-low-, low-, or intermediate-risk myelodysplastic syndromes. One hundred seventy-three patients were randomized 1:1 to DT (n = 86) or FCT (n = 87). Adverse events (overall), consistent with the known deferasirox safety profile, were reported in similar proportions of patients for each formulation (DT 89.5%; FCT 89.7%), with a lower frequency of severe events observed in patients receiving FCT (19.5% vs. 25.6% DT). Laboratory parameters (serum creatinine, creatinine clearance, alanine aminotransferase, aspartate aminotransferase and urine protein/creatinine ratio) generally remained stable throughout the study. Patient-reported outcomes showed greater adherence and satisfaction, better palatability and fewer concerns with FCT than DT. Treatment compliance by pill count was higher with FCT (92.9%) than with DT (85.3%). This analysis suggests deferasirox FCT offers an improved formulation with enhanced patient satisfaction, which may improve adherence, thereby reducing frequency and severity of iron overload-related complications.

A Multiparticulate Delivery System for Potential Colonic Targeting Using Bovine Serum Albumin as a Model Protein : Theme: Formulation and Manufacturing of Solid Dosage Forms Guest Editors: Tony Zhou and Tonglei Li.

PURPOSE: There are many important diseases whose treatment could be improved by delivering a therapeutic protein to the colon, for example, Clostridium difficile infection, ulcerative colitis and Crohn's Disease. The goal of this project was to investigate the feasibility of colonic delivery of proteins using multiparticulate beads. METHODS: In this work, bovine serum albumin (BSA) was adopted as a model protein. BSA was spray layered onto beads, followed by coating of an enteric polymer EUDRAGIT® FS 30 D to develop a colonic delivery system. The secondary and tertiary structure change and aggregation of BSA during spray layering process was examined. The BSA layered beads were then challenged in an accelerated stability study using International Council for Harmonization (ICH) conditions. The in vitro release of BSA from enteric coated beads was examined using United States Pharmacopeia (USP) dissolution apparatus 1. RESULTS: No significant changes in the secondary and tertiary structure or aggregation profile of BSA were observed after the spray layering process. Degradation of BSA to different extents was detected after storing at 25°C and 40°C for 38 days. Enteric coated BSA beads were intact in acidic media while released BSA in pH 7.4 phosphate buffer. CONCLUSION: We showed the feasibility of delivering proteins to colon in vitro using multiparticulate system.

Self-assembled polyelectrolyte complexes films as efficient compression coating layers for controlled-releasing tablets.

Currently, polysaccharide-based hydrogels are widely studied macromolecular networks to modify drug dissolution from controlled-releasing matrix tablets. Among them, polyelectrolyte complexes (PEC) films consisted of chitosan (CS) and sodium alginate (SA) could be obtained via spontaneously assembling under physiological gastrointestinal environment. Here, we utilized these self-assembled PEC films as an efficient coating materials to develop controlled-released matrix tablets through compression coating process, with paracetamol (APAP) as model drug. The constitutive and morphology characteristic studies on these PEC films illustrated that the mixture of CS and SA with the weight ratio of 1:1 would be an promising outer layer for compression-coating tablets. In addition, the in vitro drug releasing behavior experiments demonstrated that the optimized compression coating tablets displayed satisfied zero-order drug releasing profits. Furthermore, the in vivo pharmacokinetic studies of these APAP loaded compression-coated tablets in New Zealand rabbits gave that the Tmax (12.32 ± 1.05 h) was significantly prolonged (p < 0.01), compared to that (0.89 ± 0.26 h) of common APAP tablets (Jinfuning®) after oral administration. These studies suggest that the compression-coated tablets with self-assembled PEC film as coating outer layer may be a promising strategy for peroral controlled release delivery system of water soluble drugs.

Preparation and evaluation of enteric coated tablets of hot-melt extruded lansoprazole.

The objective of this work was to use hot-melt extrusion (HME) technology to improve the physiochemical properties of lansoprazole (LNS) to prepare stable enteric coated LNS tablets. For the extrusion process, we chose Kollidon® 12 PF (K12) polymeric matrix. Lutrol® F 68 was selected as the plasticizer and magnesium oxide (MgO) as the alkalizer. With or without the alkalizer, LNS at 10% drug load was extruded with K12 and F68. LNS changed to the amorphous phase and showed better release compared to that of the pure crystalline drug. Inclusion of MgO improved LNS extrudability and release and resulted in over 80% drug release in the buffer stage. Hot-melt extruded LNS was physically and chemically stable after 12 months of storage. Both formulations were studied for compatibility with Eudragit® L100-55. The optimized formulation was compressed into a tablet followed by coating process utilizing a pan coater using L100-55 as an enteric coating polymer. In a two-step dissolution study, the release profile of the enteric coated LNS tablets in the acidic stage was less than 10% of the LNS, while that in the buffer stage was more than 80%. Drug content analysis revealed the LNS content to be 97%, indicating the chemical stability of the enteric coated tablet after storage for six months. HME, which has not been previously used for LNS, is a valuable technique to reduce processing time in the manufacture of enteric coated formulations of an acid-sensitive active pharmaceutical ingredient as compared to the existing methods.

Quantitative Appearance Inspection for Film Coated Tablets.

The decision criteria for the physical appearance of pharmaceutical products are subjective and qualitative means of evaluation that are based entirely on human interpretation. In this study, we have developed a comprehensive method for the quantitative analysis of the physical appearance of film coated tablets. Three different kinds of film coated tablets with considerable differences in their physical appearances were manufactured as models, and their surface roughness, contact angle, color measurements and physicochemical properties were investigated as potential characteristics for the quantitative analysis of their physical appearance. All of these characteristics were useful for the quantitative evaluation of the physical appearances of the tablets, and could potentially be used to establish decision criteria to assess the quality of tablets. In particular, the analysis of the surface roughness and film coating properties of the tablets by terahertz spectroscopy allowed for an effective evaluation of the tablets' properties. These results indicated the possibility of inspecting the appearance of tablets during the film coating process.

Novel application method of talcum powder to prevent sticking tendency and modify release of esomeprazole magnesium enteric-coated pellets.

Actually, reflecting drug release from polymer-coated pellets remains a challenge. In this study, sticking of pellets caused by Eudragit®L30D-55 was observed during the release process, leading to change in drug release. Talcum powder (talc) was used in esomeprazole magnesium pellets to prevent sticking and modify release of pellets. Three methods including talc incorporated in enteric layer, physically mixed and coating resulted pellets were employed to prevent the sticking. The release of pellets was modified by addition talc into subcoat. The dispersion coefficient (Fd) and release profiles were determined in phosphate buffer solution (pH 6.8 and 6.0) and distilled water. It was found that the first manner made Fd increase to about 0.75, but the latter two methods could completely prevent sticking. Also, the second manner was more simple and readily scaled up. In addition, talc in subcoat significantly slowed the drug release in water, but the slowing release effect is less pronounced at pH 6.0 and 6.8. These different effects of talc were attributed to a different release mechanism in three media. The release profiles in water were fitted to Nuttanan model, and the K designated as "diffusive resistance constant" was linearly increased with talc levels in subcoat (R(2)=0.9874).

Rapid Assessment of Tablet Film Coating Quality by Multispectral UV Imaging.

Chemical imaging techniques are beneficial for control of tablet coating layer quality as they provide spectral and spatial information and allow characterization of various types of coating defects. The purpose of this study was to assess the applicability of multispectral UV imaging for assessment of the coating layer quality of tablets. UV images were used to detect, characterize, and localize coating layer defects such as chipped parts, inhomogeneities, and cracks, as well as to evaluate the coating surface texture. Acetylsalicylic acid tablets were prepared on a rotary tablet press and coated with a polyvinyl alcohol-polyethylene glycol graft copolymer using a pan coater. It was demonstrated that the coating intactness can be assessed accurately and fast by UV imaging. The different types of coating defects could be differentiated and localized based on multivariate image analysis and Soft Independent Modeling by Class Analogy applied to the UV images. Tablets with inhomogeneous texture of the coating could be identified and distinguished from those with a homogeneous surface texture. Consequently, UV imaging was shown to be well-suited for monitoring of the tablet coating layer quality. UV imaging is a promising technique for fast quality control of the tablet coating because of the high data acquisition speed and its nondestructive analytical nature.

Compression-Coated Tablet for Colon Targeting: Impact of Coating and Core Materials on Drug Release.

This work was envisaged to develop compression-coated tablets using a blend of Ca(+2) ion cross-linked carboxymethyl xanthan gum (CMXG) and sodium alginate (SAL) for delayed release of immediate pulse release tablets of prednisolone (PDL) in the colon without the need of colonic bacterial intervention for degradation of the polysaccharide coat. The core tablets containing PDL and other compatible excipients were prepared by direct compression method and subsequently compression coated with different ratios of CMXG and SAL. Long T lag, the time required to restrict the drug release below 10%, and short T rap, the time required for immediate release following the T lag, were considered as suitable release parameters for evaluation of colon targeting of PDL tablets. Among the various compression coats, a blend of CMXG and SAL in a ratio of 1.5:3.5 provided T lag of 5.12 ± 0.09 h and T rap of 6.50 ± 0.05 h. The increase in microcrystalline cellulose (MCC) and crospovidone (CP) in the core tablets did not change T lag significantly although decreased the T rap marginally. Inclusion of an osmogen in the core tablets decreased the T lag to 4.05 ± 0.08 h and T rap to 3.56 ± 0.06 h. The increase in coat weight to 225 mg provided a reasonably long T lag (6.06 ± 0.09 h) and short T rap (4.36 ± 0.20 h). Drug release from most of the formulations followed the Hixson-Crowell equation and sigmoidal pattern as confirmed by the Weibull equation. In conclusion, tablets, compression coated with CMXG and SAL in a ratio of 1.5:3.5 and having 225-mg coat weight, were apparently found suitable for colon targeting.

A Novel Approach to Flurbiprofen Pulsatile Colonic Release: Formulation and Pharmacokinetics of Double-Compression-Coated Mini-Tablets.

A significant plan is executed in the present study to study the effect of double-compression coating on flurbiprofen core mini-tablets to achieve the pulsatile colonic delivery to deliver the drug at a specific time as per the patho-physiological need of the disease that results in improved therapeutic efficacy. In this study, pulsatile double-compression-coated tablets were prepared based on time-controlled hydroxypropyl methylcellulose K100M inner compression coat and pH-sensitive Eudragit S100 outer compression coat. Then, the tablets were evaluated for both physical evaluation and drug-release studies, and to prove these results, in vivo pharmacokinetic studies in human volunteers were conducted. From the in vitro drug-release studies, F6 tablets were considered as the best formulation, which retarded the drug release in the stomach and small intestine (3.42 ± 0.12% in 5 h) and progressively released to the colon (99.78 ± 0.74% in 24 h). The release process followed zero-order release kinetics, and from the stability studies, similarity factor between dissolution data before and after storage was found to be 88.86. From the pharmacokinetic evaluation, core mini-tablets producing peak plasma concentration (C max) was 14,677.51 ± 12.16 ng/ml at 3 h T max and pulsatile colonic tablets showed C max = 12,374.67 ± 16.72 ng/ml at 12 h T max. The area under the curve for the mini and pulsatile tablets was 41,238.52 and 72,369.24 ng-h/ml, and the mean resident time was 3.43 and 10.61 h, respectively. In conclusion, development of double-compression-coated tablets is a promising way to achieve the pulsatile colonic release of flurbiprofen.

Evaluation of coating properties of enteric-coated tablets using terahertz pulsed imaging.

PURPOSE: Enteric coatings are used to reduce gastrointestinal side effects and control the release properties of oral medications. Although widely used, the effect of formulation and process conditions on physicochemical and functional properties of enteric coatings remains unclear. METHODS: Terahertz pulsed imaging (TPI) was employed to evaluate the coat properties of enteric coated tablets (ECTs) with various acid resistance. Other analytic methods, such as loss on drying, scanning electron microscopy and X-ray computed tomography were then used to validate the relationships established among 4 TPI-derived parameters and the physicochemical properties of enteric coatings. RESULTS: Weight gain measurement did not provide any information to assess acid resistance of enteric coating, whereas four TPI-derived parameters non-destructively reflected the coating properties such as thickness, coat uniformity, density, and water distribution, allowing the identification of the causes of poor acid resistance in certain ECT batches using a single measurement. These parameters also revealed the effect of coating conditions; in particular, coating under dry conditions led to less dense and nonuniform coatings with poor acid resistance. CONCLUSION: We demonstrated the utility of TPI to identify structural defects within ECTs with poor acid resistance. TPI-derived parameters can aid in formulation development and quality control of ECTs.

Evaluation of the pharmaceutical characteristics of various enteric-coated aspirin tablets under different storage conditions.

The formulation characteristics of 6 brands of enteric-coated aspirin tablets under unpackaged conditions at 40°C and 60°C for 4 weeks were analyzed. Appearance, salicylic acid content, dissolution rates, and surface properties (by Raman microscopy) were evaluated to determine stability data, taking into account the clinical use of generic drugs. No change in appearance, decomposition, or dissolution rates was observed in unpackaged aspirin tablets stored at 40°C for 4 weeks. However, when stored at 60°C, tablets of 5 of the 6 brands showed whiskers on their surfaces along with an increase in salicylic acid content and a decrease in dissolution rate. Results of Raman mapping on the surface and cross sectional surface of the tablets with whiskers showed a salicylic acid peak associated with storage at 60°C for 4 weeks. However, for tablets from 1 of the 6 brands, no salicylic acid peaks were observed. For this tablet, Raman microscopy revealed 2 layers of film coating, and talc, which greatly affected the stability of the acetylsalicylic acid, was found only in the outer layer film. These results indicated that the protection of compatibility with talc is one of the important factors in enhancement of aspirin tablet stability in this tablet. We concluded that certification of the characteristics associated with stability and formulation is essential for generic drugs, which are not required to undergo stability testing under extreme storage conditions.