
The aim of this study was to determine what combination of ingredients, this translates into a tablet core that would be suitable for use in a aqueous enteric film coating / A>. A relatively simple formulation of microcrystalline cellulose (MCC) and partly pregelatinized starch (PGS-P) was found to provide the necessary properties. MCC at formulation, provided that the compactness needed to produce a tablet bearing the mechanical process of film coating. P-PGS provides dissolution characteristics and is responsible for the stability characteristics of this moisture-sensitive, application of film enteric coating. It was also found that the P-PGA could be used to reduce the harmful effects of superdisintegrants formulations.
In recent years, aspirin (ASA, also known as aspirin) was prescribed a variety of indications. Besides its use as an analgesic, antipyretic and anti-inflammatory, ASA is not indicated for use in the prevention and treatment of heart disease and stroke. Other studies are currently investigating the possibility of ASA to strengthen the immune system, treatment of cognitive decline and reduce the risk of colon and ovarian cancer. A small daily dose 75-81 mg, is commonly used in preventive therapy ASA. Historically, the AEA has been considered a potential gastric irritation (1), and studies have shown that the incidence of intestinal gastric side effects may increase with regular use (2) enteric-coated tablets is therefore desirable to avoid distortions or stomach irritation that daily ASA therapy.
Aspirin is a medicine sensitive to moisture and can be hydrolyzed into acetic acid and salicylic acid when exposed to high humidity and high temperatures (3). Since the coating process ASA tablets are both high temperatures and humidity, it is important that the formulation is resistant to moisture interaction. Mitrevej Hollenbeck and discovered that a field is generated around hydrophilic ASA crystals under conditions of high humidity and that is the combination of the SAA with some disintegrants hydrophilic near the glass condensation can occur ASA (4). The disintegrants were studied sodium starch glycolate (SSG), croscarmellose sodium (CCS), crospovidone and colloidal silica. During the process of film coating, aqueous Faroongsarng Peck and determined that the depth of water penetration into the core of the tablet could be directly related to the concentration and type of decay used in the formula (5). Work continued on Bashar Al-aqueous coating tablets Taani ASA study confirmed that the humidity during the coating process depends not only, but the wording could be directly related to the stability of the final coated ASA tablets (6).
A review of the ingredients in five products purchased commercially ASA noted that, in most cases, were the main ingredients of microcrystalline cellulose (MCC) and some form of starch. The use of additional ingredients include disintegrants (eg lubricants CCS and SSG), and glidants varied. The five products were packaged in sealed high density polyethylene (HDPE), three of which contained carbon / silica desiccant packs. The aim of this study was to determine what combination of ingredients found in commercial products ASA would result in a tablet core that would be suitable for use in a process of aqueous enteric coating film. Ideally, enteric coated tablets should have excellent stability in accelerated storage conditions without the fuse more (and more expensive) precautions such as packaging desiccant packets for other special packaging materials.
material
Aspirin
1040 (USP 40-mesh aspirin crystals, Rhodia, Cranbury, New Jersey, USA) was used as active material. The excipients used in the study were partially pregelatinized starch (PGS-P) (Starch 1500, Colorcon, West Point, Pennsylvania, USA), MCC (Emcocel 50M, Penwest, Patterson, New York, USA) SSG (Explotab, Penwest), CCS (Ac-Di-Sol, FMC, Princeton, New Jersey, USA) and stearic acid NF (vegetable powder purified OLEOTEC Ltd, London, UK). The materials used were 85 ml container with aluminum seal HDPE bottles (plastic and glass Drug Co., Boyertown, Pennsylvania, USA) and desiccant (3964, Sud-Chemie Performance Packaging, Belen, New Mexico, USA. UU.). Coating materials used were an aqueous enteric coating system (Opadry II), both produced by Colorcon.
dry ingredients are mixed in a blender 16 / 4 with double wall (Patterson-Kelley Co., East Stroudsberg, Pennsylvania, USA). The tablets have been compressed into an instrumented 10 station Piccola rotary press (Riva, Buenos Aires, Argentina). tablet strength was measured with a tester Multichek (Erweka, Milford, Connecticut, USA). A team of 15-inch vented coating (layer II, O’Hara Technologies, Toronto, Canada) was used for coating. A dissolution test station (VK 7010, the team VanKel, Cary, North Carolina, USA) was used to test the drug issue. An HPLC (high performance liquid chromatography system (Alliance 2690, Waters Corp., Milford, MA, USA) was used to determine the concentration of salicylic acid free.
Methods Tablet Mixing and Preparation
formulations (see Table I) consisting of constant levels of ASA and the oil and various levels of MCC, PGS-P, CCS and SSG were mixed dry for 15 minutes each in a blender with double wall . The lot size of each mixture is 5kg. Each of the six mixtures are then compressed against the press, 10-station rotary tablet 7. 0 mm concave standard tools. The weight was 162 tablets of destiny. 0 mg and the compaction force was adjusted to produce tablets with a tensile strength of 6. 0-7. Kp 0. The tablet coating was performed on a 15-inch skillet with side vents with a gun. The tank load is 3 kg. A putty Opadry II dispersed in water (15% w / w) was applied to obtain a theoretical gain weight 2% compressed tablets of the six lots. stucco application was immediately followed by an enteric coating consisting Sureteric dispersed in water (15% w / w) and applied to obtain a theoretical weight gain of 10%. A finished Opadry II dispersed in water (15% w / w) is then applied to the tablets of a weight gain of 2%. The six trials were conducted coating using the same process temperatures recommended spray rates and conditions. In general, the use of fill under the enteric coating is optional and depends largely on the quality of the tablet core. As the six batches contained different ingredients, a filler has been applied to all six games so they do not change the level of small bowel changes on the surface of the tablet. The use of a finish is optional, but many commercial products have a finish applied to the base color.
Dissolution and free salicylic acid Test
without proof solution and salicylic acid were performed according to the USP 23 monograph for tablets ASA. The tablets were tested according to USP 23 monograph for delayed-release tablets of ASA.
Tablet Hardness Testing
uncoated
were tested for diametral breaking strength before and after storage under conditions of acceleration. The average result was reported by 20 tablets of the test.
Samples without coating of each formulation were packaged in bottles of high density polyethylene (120 tablets per bottle). coated tablets of each formulation were packed in the same way: a set of samples were packaged without desiccant, a second group of samples was packed with a desiccant pack in every bottle. All bottles were induction (aluminum), sealed and stored under conditions of acceleration-40 degrees Celcius/75% relative humidity (RH) for 3 months.
Results
acetate buffer (pH = 4. 5) revealed that only Lot A, containing only MCC as an excipient did not reach 80% drug release within 20 min. The results of the dissolution after storage in accelerated conditions showed little change from the first test.
most significant were the results of the tablet mechanical strength after exposure to accelerated temperature and humidity conditions. The tablets containing MCC AAS and only lost eight. 57% in tablet hardness, whereas the plates with combinations of MCC-PGS-P showed the least decrease in tablet hardness, 3. 0% loss. The application of a special safeguard or in combination with CCM CCS led to a loss of more than 36. 3% in tablet strength. Interestingly, when the same levels of CCS and SSG tables were used to combine P-PGA and MCC, the loss of tablet hardness was less deep. Comparing the levels of salicylic acid in tablets are not covered in the initial time point and after 3 months to 40% RH Celcius/75 degrees, the results showed a similar trend as tablet hardness results.
The limit for free
USP salicylic acid tablets coated ASA does not exceed 0. 3%. After three months on accelerating the tablets containing only MCC as an excipient or MCC or both SSG CCS shows a significantly increased risk of salicylic acid and not to satisfy the USP. The combination of MCC-P-PGS ASA has virtually no degradation with storage time under adverse conditions, and the increase of salicylic acid was negligible.
demonstrated that P-PGA used in this study has a tendency to absorb moisture is less than or CCS SSG and consume less moisture in the form of tablets under high humidity (7). This may explain some of the positive effects observed with the use of this formulation. The data also suggest that the P-DGP may be able to trap and retain moisture within the formulation, thus delaying moisture interaction with ASA.
Initial results
after coating, the tablets of all formulations had a good look. None of the tablets exhibited any signs of defects during or after testing is complete. Tables of all batches passed the testing phase of acid solution, without release of ASA after 2 hours at 0. 1 N HCl. During the test phase buffer (pH = 6. 80, coated tablet dissolution results, only tablets containing only MCC and ASA did not meet USP specifications not less than 80% ASA released in 90 min. In fact, other five formulations reached 80% of ASA release in less than 20 min.
Showing
compressed Stability
After three months of storage at 40% RH Celcius/75 degrees, some of the tablets containing SSG exposed CCS or softening of the film coating of tablets and bonded together in jars HDPE. This occurred in the samples that were prepared with and without desiccant. The tablets that shows signs of defects at this point it was considered that the stability failures.
The results of salicylic acid-coated tablets were very similar to those for uncoated results. The USP limit for salicylic acid free coated tablets ASA 3. 0%, is higher than the specific coated tablet. After three months in acceleration, tablets containing MCC as an excipient only had higher, but acceptable, levels of salicylic acid. The combination of MCC with the CAC or SSG resulted in substantial increases of over 5. 0% of total salicylic acid, so they do not comply with the USP. Again, the most acceptable results were observed for tablets containing MCC and PGS-P as excipients, which showed no increase in salicylic acid was used as desiccant and only 0. 91% increase when packaged without desiccant. The addition of P-PGS substantially reduced the amount of degradation of ASA in tablets containing MCC with SSG or CCS, which had unacceptable levels of salicylic acid.
“It was interesting to note that the addition of desiccant to the bottles was not enough to eliminate or substantially reduce the negative effects of superdisintegrants. Of the six formulations, tablets containing MCC alone or the combination of MCC-P-excipient PGS met the desired performance requirements of a stable of good appearance, resistance to acids and acceptable levels of salicylic acid. The formulation with only MCC did not meet the requirements of slow-release ASA in buffer solution for the first time or after 3 months storage conditions of acceleration. The tablets containing the combination of MCC-P-DGP has shown excellent results delayed release dissolution initially and after 3 months to 40 degrees Celcius/75% relative humidity.
Conclusions
The results obtained in this study gave a relatively simple ASA using a combination of MCC and PGS-P as main ingredients. MCC in the formulation provides sturdiness required to produce a tablet that must withstand the mechanical process of film coating. Starch offers features needed in this moisture-sensitive solution, application of the enteric coating film. The formulation without the use of additional superdisintegrants would be very suitable for the process of film coating, aqueous film-coated finish, requires no special packaging materials. It was also found that the P-PGA could be used to reduce the harmful effects of superdisintegrants formulations. This would also reduce the cost of raw materials. The next phase of this study will focus on improving the levels required for enteric coating and scale-up of the enteric coating process.
Thanks
The authors thank Rhodia Inc. for the donation of AEA used in this project. And thanks to Mr. David Ferrizzi Colorcon its analytical support.
Article reproduced
May 2001 Pharmaceutical Technology Europe. Reprint Publication number: 0462. To view accompanying tables and figures, please visit http://www. Colorcon. com / literature / marketing / ex / starch 1500/enteric_articlenc. pdf.
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Merck Index, twelfth edition, 886, Merck Research Laboratories (1996).
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Faroongsarng D. , G. Peck, The swelling of core tablets during aqueous layer I: A simple description of inflammation Extension and the penetration of water soluble tablets containing an Superdisintegrant, “Drug Dev. Ind. Pharm. 17 (18) 2439-2455 (1991).
B. Taani to “the physical interaction of the aqueous coating of tablet cores containing aqueous pharmaceutical superdisintegrants for Coatings,” Ph.D. Thesis, Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, Indiana, USA (May 1999).
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