Average Disintegration Research Articles

Physicochemical Evaluation of Brands of Amlodipine Besylate Tablets.

Background: Hypertension is a chronic condition, and the cost of filling prescriptions has a potential of putting a financial strain on patients, hence the need for lower priced but bioequivalent generics. The Nigerian drug market is awash with generics of Amlodipine besylate, a first line drug in the treatment of hypertension, therefore, any prescribed alternative must be bioequivalent to the originator. Objectives: This study assessed the physicochemical properties of some brands in order to predict pharmaceutical and bioequivalence and invariably, the interchangeability with the innovator brand. Methods: Compendial parameters of average weight, friability, disintegration, drug content and dissolution profile of ten generic brands were evaluated using the United States Pharmacopeia (USP) as well as the non-official hardness test. Results: Two brands failed the test for hardness, while still keeping to the stipulated friability limit. All the brands met the required disintegration time, irrespective of the discordance of some brands in the breaking force and friability values. All brands were found to contain between 92.00 and 103.57% (w/w) of Amlodipine besylate. Two brands failed to achieve ≥75% dissolution expected at 30 minutes and this was reflected in the low f2 values of 35.06% and 28.73%. The dissolution curves displayed a similarity for two brands, which was also corroborated by the high percentage dissolution efficiency (DE) of 92.00%, as well as the f1 and f2 values, compared to the innovator brand. Conclusion: Although the parameters used may predict therapeutic equivalence, interchangeability with the comparator brand is subject to relevant bioequivalence studies.

Physical Characteristics of Probiotic Effervescent Tablets with Various Concentration of Maltodextrin as Coating Materials

The application of RICA (Research Institute for Coastal Aquaculture) liquid probiotic bacteria proved to be able to prevent attacks of both types of vibriosis disease and White Spot Syndrome Virus (WSSV) through improved pond water quality. This RICA liquid probiotics is coated using maltodextrin with 3 variations of concentration which are then formed into probiotic effervescent tablets. Apart from making it easy to distribute, this solid probiotic is easily applied without fermentation such as the use of liquid probiotics. The aims of this study was to determine the physical characteristics of probiotic effervescent tablets from maltodextrin coatings with different concentration. The concentration maltodextrin as coating materials were is 20%, 30% and 40% (b/v). The parameters test are average weight, friability, hardness and disintegration time. The results showed that the effervescent tablets of probiotics with a concentration of maltodextrin 40% had a mean weight higher than other concentrations at 798.88 mg. While the effervescent tablets of probiotic with a maltodextrin concentration of 20% had a lower friability and disintegration time compared to other concentrations of 0.05% and 12.96 minutes. And has a higher level of hardness that is equal to 10.89 N compared to other concentrations that is 30% and 40% concentration maltodextrin. The concentration of 20% maltodextrin was the best treatment of this study.

Design and characterization of taste masked metronidazole microcapsules and its utilization in the formulation of orodispersible tablets

Orodispersible tablet (ODT) containing microcapsules is an advanced and convenient drug delivery system that offers advantages of easy administration, and increased bioavailability. Metronidazole is an antiprotozoal, with a bitter and metallic taste as its major drawback. A taste masking is required since the tablet will disintegrate in the oral cavity releasing the drug into close proximity to the taste buds. The purpose of the study is to design and evaluate metronidazole microcapsules for formulation of taste masked orally ODT metronidazole tablets. Taste masked metronidazole microcapsules were prepared by emulsion polymerization method with sodium alginate as polymer using different drug to polymer ratio. The microcapsules were evaluated for drug loading, entrapment efficiency, drug-polymer interaction by FTIR spectrometry, DTA, and flow properties. Batches B4 and B5 were formulated into orally disintegrating tablet by direct compression method. The results of FTIR spectrometry and DTA characterization of microcapsules revealed absence of drug-polymer interaction. Evaluation of the microcapsules showed fairly good flow properties and increase in entrapment efficiency as the polymer concentration increased. Evaluation of the directly compressed ODTs showed acceptable weight variation, and average disintegration time less than 60 sec. The average tablet crushing strength range from 18 to 19 N, and the drug release profiles showed greater than 80% release of metronidazole within 10 min. The successful microencapsulation of metronidazole, fast disintegration, rapid drug release profile, and evidence of compatibility between metronidazole and the process polymer demonstrates the suitability of the microcapsules for formulation of orally disintegrating tablet for convenient delivery of metronidazole.Keywords: Orally disintegrating tablets, microencapsulation, taste masking

The Use of Disintegration Ratio in Evaluating Rock Durability in Selected Mudrock Samples in Indonesia

Characterization of durability of mudrocks is important regarding its slaking behaviour within a short time when exposed to and or interact with water. Some relevant cases that occurred due to slaking are damage to roads and slope failures along the Cipularang and Cipali Toll Road. Current engineering activities related to the presence of mudrocks are being and will be held in several locations in Indonesia such as the construction of the Cisumdawu Toll Road in Ujungjaya District, Sumedang and building the National Observatory in Timau District, Kupang. This research is useful for providing engineering considerations related to those activities.
 The methods used in this research included X-ray diffraction to obtain mineralogy of mudrock, laboratory testing of physical properties of rocks such as dry density, water content, porosity, absorption and mudrocks durability tests. Durability of rocks was determined by disintegration index test. Testing was carried out by wetting and drying of rock samples.
 Test results showed that the average disintegration ratio of claystones, shales, mudstones and siltstones are 0.1035, 0.2183, 0.4942 and 0.9900. Slaking mode occurs to claystones, mudstones and shales is body slaking while dispersion slaking occurs to siltstones. Evaluation of the durability of mudrocks in this research indicates that siltstones have the highest durability characterized by very slow disintegration, followed by mudstones, shales and claystones at the lowest with very quick disintegration. Disintegration ratio from the disintegration index test characterizes the durability of mudrocks in more details. It can be concluded that porosity and absorption are incorporated into the main factors affecting the durability of mudrocks.

Physico-chemical properties and antibacterial drug performance of amoxicillin from streets in Bamenda, Cameroon

Background: The advent of microbial drug resistance creates a concern about the quality of anti-infective drugs. The rise in some microbial resistance to therapy has urged us to investigate physico-chemical properties and antibacterial performance of amoxicillin from streets in Bamenda, Cameroon.Methods: Amoxicillin samples were purchased from street vendors in Bamenda. Cameroon. Visual inspection was done for defects and signs of discoloration, deterioration or other physical disfiguration. Weight uniformity test for each sample of antibiotic tablet was carried out. The time for drug disintegration for each sample of amoxicillin was evaluated. Microbial antibiotic susceptibility tests were done using both the agar disc diffusion and micro well broth dilution methods to check drug performance. Data analysis was done and comparison checked with Student-Newman-Keuls at p<0.05.Results: The mean weight of amoxicillin drugs ranged from 632.00±11.5 to 748.06±17.9 mg. Tablets from Austria had a significant decrease in weight compared to those from Germany and Nigeria. This was similar with the capsules from India and China. Average disintegration varied significantly from as small as 2.2 to 14.4 minutes. All the amoxicillin samples were active against the tested bacteria with mean zones of inhibitions ranging from 8.33±0.57 to 39.33±0.57 mm. The MICs and MBCs values range from 1 to 64 µg/ml. For the same bacterium the growth inhibitory effects of the various drugs were not all similar.Conclusions: Some of the amoxicillin samples studied in this paper showed significant differences in their weights and performances (antibacterial activities). Probably the required amount of API was not respected.

Evaluation of the nimesulide content in splitting tablets

Nimesulide is a non-steroidal anti-inflammatory drug (NSAID) that inhibits the action of the enzyme cyclooxygenase-2 and is widely used in many countries for the treatment of pain and inflammation. It is often given on a dosage adjustment basis mainly in the elderly and children. In the present work the nimesulide tablet splitting process from three different suppliers was studied using a tablet cutter in order to verify the influence of the breakdown of the same on the content of each obtained fragment. The tests of average weight, hardness, friability, disintegration, dosage and uniformity of unit doses were performed following the official methodology established by the Brazilian Pharmacopoeia. The samples studied met the official specifications before being submitted to the partition procedure; however, after dividing the tablets, the drug content in the halves presented excessive variation, showing that this procedure should not be performed for the drug Nimesulide. In cases of need for varying administration doses of Nimesulide, it is recommended that the drug be manipulated or that another pharmaceutical form is used in order to ensure dosage in each unit of the dosage form.

DEVELOPMENT OF HERBAL CAPSULES CONTAINING MULBERRY LEAF AND BLACK TEA EXTRACTS USING THE MODIFIED LIQUISOLID TECHNIQUES

Objective: The objective of this study was to develop the capsules containing mulberry leaf extract (MLE) and black tea extract (BTE).
 Methods: MLE and BTE were prepared by maceration and determined for phytochemicals, in vitro alpha-amylase and alpha-glucosidase inhibitory activities using the enzymatic colorimetric assay. The granules of MLE and BTE were prepared by the application of liquisolid technique and evaluated for the flow properties. The selected granule formulation was filled into the hard gelatin capsule and evaluated for weight variation and disintegration.
 Results: The yields of MLE and BTE solid extracts were 8.12 and 4.23% w/w, respectively. Total phenolic and total flavonoid contents were 32.46±5.22 mg TAE/g DW and 44.03±3.37 mg QE/g DW for MLE and 244.66±23.28 mg TAE/g DW and 214.43±3.22 mg QE/g DW for BTE, respectively. The IC50 for alpha-amylase of MLE and BTE were 0.69±0.04 and 3.34±0.08 mg/ml, respectively; whereas those for alpha-glucosidase of MLE and BTE were 0.67±0.42 and 0.43±0.15 mg/ml, respectively. The granule prepared with MCC and silica at the ratio of 20:1 showed the highest flowability. The weight variation of the prepared MLE and BTE capsules was within the range of the limitation criteria of ±5%. The average disintegration time of capsules was 1.1±0.1 min.
 Conclusion: Herbal capsules of MLE and BTE were successfully prepared. The suitable carrier and coating were MCC and silica with a ratio of 20:1. This study revealed the potential application of liquisolid technique as a tool to produce a capsule of herbal crude extracts.

Iceberg drift and ocean circulation in the northwestern Weddell Sea, Antarctica

Icebergs are distinctive features in the Southern Ocean and can influence the physicochemical properties of the ocean environment around them. Their trajectories are influenced by ocean currents, sea ice, bathymetry and wind action. Here, twenty-five icebergs were identified and tracked by applying image classification methods to a series of 142 Advanced Synthetic Aperture Radar (ASAR) images obtained during 2008 and 2009. Tracking these icebergs made it possible to associate the patterns of iceberg drift with the main ocean currents and front systems in this region, including the Antarctic Coastal Current, the Antarctic Slope Front and the Weddell Front. A case study investigated here revealed the recirculation of a Weddell Sea iceberg within the Bransfield Strait in the Northern Antarctic Peninsula as well as its corresponding mass loss starting in the Weddell Sea and extending throughout the monitoring period. The icebergs studied experienced an average disintegration percentage of 21.15% and an average drift speed of 0.22 ± 0.11 km h–1. The icebergs that drifted at least 500 km had an average meltwater injection rate of 62.76 ± 38.27 m3 s–1 in the ocean around the Northern Antarctic Peninsula.

THE INTERCHANGEABILITY OF DOXYCYCLINE TABLETS NOT IS TOTALLY SAFE

Doxycycline is a second-generation semi-synthetic antimicrobial of tetracyclines. It is a broad spectrum antimicrobial agent used in several countries for the treatment of diseases such as chronic prostatitis, sinusitis, syphilis, chlamydia, pelvic inflammatory disease as well as additives in animal feed to improve its growth. Doxycycline is distributed free of charge through Unified Health System in Brazil, which, according to its acquisition, for subsequent distribution, does not always guarantee the same brand. Five different brands of doxycycline tablets (the reference pharmaceutical of doxycycline, two generic and two similar products) were used for evaluation of the interchangeability of the tablets by determination of average weight, hardness, friability, disintegration, the active principle content, content uniformity and in vitro dissolution. All tablets submitted to the tests of average weight, friability, hardness and disintegration were according to specification.Tests of content uniformity show drugs out of specification, with contents higher than 105 %. In test of dissolution, there no statistically differences among the profiles. Due to the results obtained, all doxycycline tablets analyzed could not be approved by the Quality Control sector. Sectors of production, analytical development and quality control should meet to resolve this issue. The involvement of all employees in these sectors is of critical importance for solving the problem. Thus, the importance of a pharmaceutical equivalence study is important to guarantee a safe interchangeability and consequently the same therapeutic effect.

Novel tablet formulation of amorphous candesartan cilexetil solid dispersions involving P-gp inhibition for optimal drug delivery: in vitro and in vivo evaluation

Objective: The aim of this study was to develop a novel tablet formulation of amorphous candesartan cilexetil (CAN) solid dispersion involving effective P-gp inhibition for optimal drug delivery by direct compression (DC) method.Methods: To accomplish DC, formulation blends were evaluated for micromeritic properties. The Carr index, Hausner ratio, flow rate and cotangent of the angle α were determined. The tablets with and without naringin prepared by DC technique were evaluated for average weight, hardness, disintegration time and friability assessments. The drug release profiles were determined to study the dissolution kinetics. In vivo pharmacokinetic studies were conducted in rabbits. Accelerated stability studies were performed for tablets at 40 ± 2 °C/75% RH ± 5% for 6 months.Results: FTIR studies confirmed no discoloration, liquefaction and physical interaction between naringin and drug. The results indicated that tablets prepared from naringin presented a dramatic release (82%) in 30 min with a similarity factor (76.18), which is most likely due to the amorphous nature of drug and the higher micromeritic properties of blends. Our findings noticed 1.7-fold increase in oral bioavailability of tablet prepared from naringin with mean Cmax and AUC0–12 h values as 35.81 ± 0.13 μg/mL and 0.14 ± 0.09 μg h/mL, respectively. The tablets with and without naringin prepared by DC technique were physically and chemically stable under accelerated stability conditions upon storage for 6 months.Conclusion: These results are attractive for further development of an oral tablet formulation of CAN through P-gp inhibition using naringin, a natural flavonoid as a pharmaceutical excipient.

Novel oral fast-disintegrating drug delivery devices with predefined inner structure fabricated by Three-Dimensional Printing

Abstract Objectives Novel fast-disintegrating drug delivery devices with special inner structure characteristics were designed and fabricated using Three-Dimensional Printing. Methods Based on computer-aided design models, fast-disintegrating drug delivery devices containing loose powders were prepared automatically using the Three-Dimensional Printing system. The inner powder regions were prepared by depositing the binder solutions onto selected regions during the layer-printing process. Results The devices showed acceptable pharmacotechnical properties and fine hardness (63.4 N/cm2) due to the synergistic action of several binding mechanisms, but unsatisfactory friability, with 3.55% total mass loss during the friability tests. Scanning electron microscope images clearly showed that the printed regions were well bound, and that the drug particle size was reduced or individual particles could no longer be distinguished. In contrast, the unprinted regions were uncompacted, with cracks and fissures among the loose mixed powder. All the drug delivery devices disintegrated and wetted rapidly in in-vitro tests. The average disintegration and wetting times were 23.4 s and 67.6 s, respectively. Dissolution tests showed that 98.5% of the drug was released within 2 min. Conclusions Three-Dimensional Printing offers strategies for the development of novel oral fast-disintegrating drug delivery devices.

Novel oral fast-disintegrating drug delivery devices with predefined inner structure fabricated by Three-Dimensional Printing

Novel fast-disintegrating drug delivery devices with special inner structure characteristics were designed and fabricated using Three-Dimensional Printing. Based on computer-aided design models, fast-disintegrating drug delivery devices containing loose powders were prepared automatically using the Three-Dimensional Printing system. The inner powder regions were prepared by depositing the binder solutions onto selected regions during the layer-printing process. The devices showed acceptable pharmacotechnical properties and fine hardness (63.4 N/cm(2)) due to the synergistic action of several binding mechanisms, but unsatisfactory friability, with 3.55% total mass loss during the friability tests. Scanning electron microscope images clearly showed that the printed regions were well bound, and that the drug particle size was reduced or individual particles could no longer be distinguished. In contrast, the unprinted regions were uncompacted, with cracks and fissures among the loose mixed powder. All the drug delivery devices disintegrated and wetted rapidly in in-vitro tests. The average disintegration and wetting times were 23.4 s and 67.6 s, respectively. Dissolution tests showed that 98.5% of the drug was released within 2 min. Three-Dimensional Printing offers strategies for the development of novel oral fast-disintegrating drug delivery devices.

Challenges with Dissolution Testing and Quality Assessment for Commercial Feverfew Products

The purpose of this study was to develop a suitable dissolution test for feverfew products and to investigate the parthenolide content, disintegration, and dissolution performance of several marketed feverfew products. Parthenolide content was determined by a validated HPLC method. Disintegration was tested according to the USP requirements for botanical dosage forms. A suitable dissolution test method was developed to study the dissolution performance of feverfew products. Parthenolide content varied from 0 to 0.23% among the feverfew products tested. The average disintegration times of these products were significantly different (p < 0.005) and varied from 5 to 11 min. All products containing measurable parthenolide exhibited more than 85% dissolution of parthenolide content in 1 h; however, these products exhibited substantially different dissolution profiles. In the first 10 min, one product released more than 80%, but dissolution from the two other products could not be detected at all during that time. Although not currently required by USP, dissolution testing of formulated products can be a useful tool to evaluate the quality of feverfew finished products. Patients should be cautious when changing from one brand to another because of such differences in actual parthenolide content and release performance. Manufacturers should commit to proper quality control procedures to ensure that label claims for content and dose are accurate and realistic.

Análise químico-farmacêutica do fluconazol e especialidade farmacêutica cápsula

O fluconazol, derivado triazólico, apresenta atividade antifúngica sendo indicado no tratamento de grande variedade de infecções fúngicas. Este trabalho foi desenvolvido com o objetivo de estabelecer parâmetros de controle de qualidade para a matéria-prima de fluconazol e forma farmacêutica cápsula, subsidiando a elaboração da monografia para a Farmacopéia Brasileira. A matéria-prima do fluconazol pode ser caracterizada pelos seguintes testes: aspecto, solubilidade e faixa de fusão. As impurezas do fluconazol podem ser detectadas por ensaio-limite de cloreto, sulfato, ferro, metais pesados, perda por dessecação e cinzas sulfatadas. Entre as provas de identificação pode-se reconhecer o fármaco por reações químicas de grupos funcionais e por técnicas instrumentais. Para determinação quantitativa do fluconazol na matéria-prima, empregou-se a volumetria com ácido perclórico, em meio acético e detecção do ponto final por indicadores e a espectrofotometria na região do ultravioleta, utilizando hidróxido de sódio 0,1 M a 261 nm. Os parâmetros estabelecidos para o controle de qualidade das amostras de cápsulas dos laboratórios analisados foram aspecto, variação do peso, desintegração, teste de dissolução e perfil de dissolução. O método de doseamento do fluconazol, na forma farmacêutica cápsula, por espectrofotometria na região do ultravioleta apresentou linearidade, especificidade, precisão e exatidão dentro dos critérios de aceitação. Os lotes dos laboratórios C, D apresentaram perfis de dissolução similares ao medicamento de referência (laboratório E), demonstrando haver um comportamento homogêneo para estes medicamentos. Os lotes dos laboratórios A e B não apresentaram homogeneidade quanto ao perfil de dissolução, quando comparado com os demais laboratórios.

Evaluation of Disintegration Testing of Different Fast Dissolving Tablets Using the Texture Analyzer

The in vitro disintegration behavior of fast dissolving systems manufactured by the main commercialized technologies was studied using the texture analyzer (TA) instrument. Quantitative parameters were employed to characterize the effect of the major test variables on the disintegration profiles. The average disintegration profiles of the products were compared using the test conditions that minimized these effects and at the same time mimicked the in vivo situation in the patient's mouth. The differences in the disintegration mechanisms of the fast dissolving systems were reflected in the shape of their disintegration profiles and in the parameters derived from the profiles. The differences were explained in relation to the technology and/or formulation characteristics involved in the manufacture of each product. The in vitro disintegration times obtained under the simulated in vivo conditions were correlated with the reported in vivo disintegration times.

Radiotelemetric Method for Evaluating Enteric Coatings In Vivo

A radiotelemetric method for the in vivo evaluation of enteric coating performance is described, and its advantages and disadvantages are compared with those of other available methods. Hydroxypropyl methylcellulose phthalate was used as the test enteric coating. Four dogs were administered several batches of enteric-coated tablets containing buffers. Tablet disintegration was determined by radiotelemetric detection of the pH drop in the upper intestine due to release of the buffer. Premature rupture of the coating in the stomach was detected by a rise and then a fall in gastric pH prior to gastric emptying. The average gastric emptying time was 80 ± 18min (SEM), while the average time for a tablet to disintegrate in the upper intestine was 14.2 ± 2min. The average disintegration time was not affected by a change in the batch (for a given tablet core pH) or the dog used, suggesting that the method yielded readily reproducible results. Although there was little correlation with in vitro disintegration times, the method gave results similar to those reported in the literature for the same enteric coating in a human study. Of the formulations tested, it was concluded that buffering the core to pH 4 was most suitable for studying enteric coating performance.

Liquid and Solid Solution Interactions of Primary Certified Colorants With Pharmaceutical Gelatins

The liquid and solid solution interactions of eight FD&C dyes in 1% concentration with pharmaceutical gelatins and the effects of the dyes on the disintegration behavior of gelatins were observed. In liquid solution by visible region spectroscopy, all FD&C dyes interacted with a type A gelatin. The xanthene dye, FD&C Red No. 3 (erythrosine), interacted to the greatest extent by a combination of ionic, hydrogen, and hydrophobic types of bonds. The FD&C dyes did not appear to interact with a type B gelatin. A method for simulating a gelatin capsule shell wall was devised to examine solid-state interactions by visible and IR-attenuated total reflectance spectroscopy, dye release patterns, and the effect of the dyes on gelatin disintegration. FD&C Red No. 3 and Violet No. 1 in solid solution appeared to interact to a greater extent than the other FD&C dyes. Hydrogen bonding changes in the solid solution films of both gelatins were not observable by IR-attenuated total reflectance spectroscopy until very high (1:10 to 1:5) dye-protein ratios were attained. The same two dyes (FD&C Red No. 3 and Violet No. 1) that showed the greatest spectral changes exhibited the slowest release times from both gelatins at temperatures both below and within the temperature range at which gelatins disintegrate and go into colloidal solution. In simulated gastric fluid USP without pepsin, the FD&C Red No. 3 dye greatly diminished the average disintegration rate of both gelatins. The addition of pepsin essentially eliminated the effect of FD&C Red No. 3 on gelatin disintegration. In simulated intestinal fluid USP without pancreatin, both gelatins disintegrated slower than in simulated gastric fluid without pepsin. FD&C Red No. 3 also had a detrimental effect on gelatin disintegration in simulated intestinal fluid without pancreatin. Pancreatin was not added to the simulated intestinal fluid because of its interference with visualization of disintegration.

Absolute Disintegration Rate of Finite Gold Sample: Determination by Coincidence Techniques

A method has been developed for absolute disintegration rate determination of finite-sized, radioactive samples. Measurements were made on a 15-mg gold foil. The average disintegration rate was 2.163X105 for 24 determinations with a precision of 2.3%. Subsequent measurements yielded precisions as low as 0.5%. Conditions of bias settings, decay corrections, and coincidence resolving times were widely varied. The scintillation, coincidence equipment, including novel pulse timing, are mentioned. Data corrections, including accidentals and particle A in detector B are discussed. It is shown that the corrections are empirical and do not limit the absolute nature of the measurements. Some of the nuclear parameter requirements and spectroscopic implications are indicated.

Cellulose Acetate Succinate as an Enteric Coating for Some Compressed Tablets

The preparation and testing of compressed tablets of barium sulfate and sodium chloride coated with cellulose acetate succinate (CAS) are described, and the statistical evaluation of the data obtained is presented. The most satisfactory coatings were obtained when the test material, in an acetone-ethyl acetate solution, was applied by a modified “pan” method using talc as a dusting powder. Generally, CAS coatings which were stable for 3 1/2 hours in Simulated Gastric Fluid USP XVI dissolved sooner than control coatings of CAP applied and treated in the same manner. Disintegration times were slightly lower for most tablets placed directly into Simulated Intestinal Fluid, USP XVI than they were for tablets first treated with Simulated Gastric Fluid USP XVI for 31/2 hours and then tested in the former solution. None of the tablet coatings showed signs of cracks as a result of storage at −2 ± 2° for 21 days or 45 ± 2° for 10 days; however, some of these showed statistically significant differences in average disintegration time when compared with samples stored at room temperature. When test and control tablets were stored at 40 ± 2° and approximately 81% humidity, the majority of coatings were unsatisfactory. Tablets lost less than 3.56% tablet weight as a result of the simulated gastric fluid treatment. Preliminary in vivo tests with human subjects indicate that CAS has merit as an enteric coating. Pancreatin appears to have little effect on the disintegration times of the test coating.

Enteric Coatings V : pH Dependence and Stability

Evidence is presented that the terms “stable in acid solutions” and “soluble in alkaline solutions” should not be applied to enteric coatings. The enteric substances studied dissolve in buffers of pH less than 7 and tablets coated with these substances disintegrate in fluids having a pH less than 7. It was demonstrated that the critical pH range in which tablets coated with styrene-maleic acid copolymer show a progressive decrease in disintegration time corresponds to a narrow pH range on either side of the pK1 of the copolymer. It is in this region that the greatest change in per cent ionization of the copolymer occurs. Relating these in vitro data with in vivo data, formerly reported, will require adjustment of current concepts of enteric coatings. It was shown that the disintegration times of tablets coated with styrenemaleic acid copolymer, dibutyl phthalate, and talc in artificial intestinal fluid, pH 6.9, changed very little after storage of the coated tablets for prolonged periods at 4°, room temperature, 40°, and 47°. Tablets coated with the other enteric compositions exhibited either decreased resistance to simulated gastric fluid or markedly increased disintegration times in artificial intestinal fluids after prolonged storage. It was demonstrated that the average disintegration time observed after storage of enteric coated tablets for one month at 47° yields an excellent prediction of the average disintegration time of the tablets after storage for two years at room temperature.