0000021782 00000 n
The determination of water content was conducted by Karl-Fischer method using the capsules content (Reference, GEL-A, GEL-B, HPMC-A and HPMC-B).15 A Karl-Fischer autotitratiom unit (Mettler, Brazil) was set up according to the manufacturer's instructions. Raj, T. J. S.; Bharati, C. H.; Ranga, K.; Raoa, K. R.; 11. 0000619171 00000 n
A.; 22. L%1O"xX'0=c`C!C
F
l*^*016~`cli`x`*p Z2]AQ W S This comparison cannot be performed with the reference medicine and HPMC capsules, because they are of different constitution. endstream
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The average values of ED% are shown in Table 3 and the graphical representation is shown in Figure 2. This test was performed for the powder mixture formulation for the development of hard gelatin and HPMC capsules. Furthermore, the compaction force used in the industry for the development of the reference may be delaying the drug release in dissolution medium. 636 76
0000549371 00000 n
0000008000 00000 n
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In the first case, the three involucres are made of hard gelatin and in the second case they are made of HPMC. 0000512245 00000 n
As gelatin has a high humidity degree (13 to 16%), hard capsules have been manufactured using a material of vegetable origin, the hydroxypropyl methylcellulose (HPMC) with the main objective of producing involucres with smaller humidity tenor (3 to 8%).6 The introduction of HPMC based capsules have appeared as an alternative to the conventional use of the hard gelatin capsules. These are important factors that must be taken into account so that the use of HPMC capsules be a viable alternative to gelatin in manipulation pharmacy and in the pharmaceutical industry for developing formulations containing ampicillin. 0000456290 00000 n
Ampicillin anhydrous reference standard (98.35%) was obtained from Brazilian Pharmacopoeia (Brazil). When the gelatin capsule is ingested, it allows the penetration of water, causing its hydration and drug release in a few min. f `
0000001853 00000 n
It is soluble in hot water and in the gastric liquid, which quickly liberates its content.3, However, main Pharmacopoeias, such as the European, Japanese and American also allow the use of other appropriate materials besides gelatin. 0000007466 00000 n
Two formulations (A and B) were developed. 0000624184 00000 n
The formulations have been differentiated according to their content, in formulation A (ampicillin trihydrate, magnesium stearate, colloidal silicon dioxide and croscarmellose sodium) and formulation B (only ampicillin trihydrate), being denominated GEL-A, GEL-B, HPMC-A and HPMC-B. 0000517248 00000 n
The water determination test showed lower humidity tenors for HPMC capsules than gelatin capsules. The collection time for the dissolution test consisted of 45 min. Capsules are solid pharmaceutical forms usually destined to the oral use that present a good acceptance for part of the population.1-3, The involucres used for the development of capsules are usually constituted by gelatin, water, coloring and other materials including preservatives and processing aids. 0000413197 00000 n
Monteiro, L. M.; Souza, A. E.; Gianotto, E. A. S.; Nery, M. M. F.; Duarte, J. C.; Freitas, O.; Casagrande, R.; Baracat, M. M.; * Regarding the dissolution test (Table 2) the hard capsules produced with gelatin showed higher percentage values of dissolution (100.18 and 101.16% for GEL-A and GEL-B, respectively) when compared to the capsules produced with HPMC (99.67 and 87.70% for HPMC-A and HPMC-B, respectively). The capsules should meet the demands of weight variation, disintegration time, assay and tenor uniformity of actives described in the monograph.12,13 Therefore, the aim of this study was to develop capsules starting from hard gelatin and HPMC involucres, to evaluate the quality of the final products and to compare them with each other and with the medicine reference. Connors, K. A.; Amidon, G. L.; Stella, V. J.; ANVISA - Agncia Nacional de Vigilncia Sanitria; 13. The analytical curve was prepared from a standard solution of ampicillin RS concentration of 100 g mL-1. 0000550107 00000 n
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0000019290 00000 n
The ampicillin used for the formulations development was weighed and the test was performed either to a specific number of taps or until the volume measured in the graduated glass cylinder changes by less than 2%, using tapped density or apparent volume tester (Pharma Test PT-TD1, Germany). This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. 0000517355 00000 n
Stability studies are necessary to evaluate the real contribution of the hard gelatin and HPMC capsules relation to the protection of drugs conditioned in these capsules. The choice of the appropriate size of the capsule for the drug to be produced is performed according to the density parameters of the powder to be encapsulated and the volume of possible capsules to be used. hb```e`X`o "l@Q6 U98=apte4Vs0^L%F}^ [&kL%:T%A JDEWSxGc^UW],;;==X{A+ $(1&%%%c @b`IA(G
PPA-7 82iaK,^14` 0000002826 00000 n
ampicillin; gelatin; hydroxypropyl methylcellulose, Evaluation of hard gelatin capsules and hydroxypropyl methylcellulose containing ampicillin, Graziella Gonalves Weigert; Anile Posser Ineu; Patrcia Gomes* e-mail: By using a forming polymer of colloidal matrix in encapsulated excipient, the dissolution of the capsule is affected promoting a controlled release.20, Several studies suggest the use of HPMC in formulations in order to promote modified releases of drugs. patriciagomes0@yahoo.com.br, , Santa Maria, The final product quality was evaluated by testing for quality control and the results were in agreement with the Brazilian Pharmacopoeia. There was no significant difference (P> 0.05) in the ED% from the capsules GEL-B (66.78%), GEL-A (60.97%) and the reference medicine (62.37%) as well as between HPMC-A (74.92%) and HPMC-B (76.18%). 0000020032 00000 n
It was observed that with increasing amounts of HPMC in the formulations it is possible to get a reduced release of the drug, which can be evidenced in the dissolution tests.23 With the use of HPMC in capsules, this polymer characteristic may promote a release different from the one observed with the capsules produced with gelatin, delaying the release of the drug and consequently modifying its kinetics of release. These results obtained are in agreement with the pharmacopoeia specifications15,16 and they show a proper process of manipulation. This instrument is suitable for testing powder Flow Time, the measurement of the cone angle (angle of repose) of the collected powder mound, measuring the weight, calculating the density and the volume of the powder cone as well as the EP/USP "Flowability" results which is to measure the flow time of 100 g of sample through a specified pouring nozzle. 0000535379 00000 n
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* @D:v2x7p01TamP,`dg`y1J O A'30hX60` % W 0000615352 00000 n
The disintegration test was carried out following the established methodology for Brazilian Pharmacopoeia15 using the disintegration tester (Pharma Test PTZ-E, Germany). The granulometric analysis of the ampicillin for the development of the capsules is an important parameter to be established; it represents a direct influence on the manipulation of the capsules in magisterial scale. Because of the delay of the drug release in initial times of the dissolution profiles, it becomes necessary to evaluate the drugs that can be conditioned in the HPMC capsules. After the completion of the angle of repose, we observed that the mixing of powders and the ampicillin alone have an angle greater than 40, which characterizes a very weak flow.5 This characteristic observed for the mixture of powders destined to the production of the capsules shows that even after the addition of a small amount of excipients to the formulation A, no improvement in the flow of powders was observed. 0000413352 00000 n
trailer
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Quality control for pharmaceutical dosage form. Thus, the problems involving hygroscopic drugs, sensitive to the humidity and with problems in their interaction with the gelatin molecules can be circumvented.6,7, The capsules produced with HPMC involucre guarantee the hygroscopic drugs stability, such as ampicillin, a bactericidal antibiotic of wide spectrum that acts against aerobic gram-negative bacteria.8,9 In the case of ampicillin, it is possible to foresee some possible degradation reactions because the ring beta-lactam is susceptible to hydrolysis (Figure 1).10,11. hbb2g`b``3
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We opted for the addition of some excipients in the formulation A, since the amount of the present drug in the formulation is not always enough to make up the chosen capsule as well as due to other characteristics of the drug. 0000517468 00000 n
Fahs, A.; Brogly, M.; Bistac, S.; Schmitt, M.; 21. Korolkovas, A.; Frana, F. F. A. C.; 10. To calculate the amount of ampicillin indeed dissolved in the medium, it was compared to that obtained with the ampicillin reference standard (RS) at concentration of 0.0022% (w/v) prepared under the same conditions. The values of relative standard deviation (RSD) of mean weight were 1.79% (reference medicine), 2.60% (GEL-A), 2.10% (GEL-B), 2.61% (HPMC-A) and 2.19% (HPMC-B). The results of mean weight, assay, disintegration time, and water determination test for the hard gelatin capsules (A and B), HPMC capsules (A and B) and reference medicine is evidenced in Table 1. 0000000016 00000 n
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In high concentrations, the linear chains of HPMC form a tangle and result in a gelatinous layer, fairly consistent, hindering the release of the active principle. 0000013371 00000 n
0000019631 00000 n
0000006128 00000 n
0000452612 00000 n
These capsules were purchased from market (Genix and Capsugel, Brazil), presenting humidity values of 13.8% (GEL) and 5.8% (HPMC), according to the certificate of analysis. This fact associated with features of ampicillin, such as increased size, density, and hygroscopic end up making the manipulation difficult because of the resistance of the flow of powders in manual encapsulator and difficulty of accommodation in the same involucres. This fact can be explained because in both comparative cases (GEL versus reference medicine and HPMC-A and HPM-B) the involucres have the same nature. The procedure performed in this technique is described in Test and dissolution profiles. (English), https://doi.org/10.1590/S0100-40422012000200010. This equipment has round sieves for particle size analysis with 8.5 or 3 inches in diameter. 0000009848 00000 n
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The time limit established for this test for hard gelatin, HPMC and the reference drug capsules was 45 min.15. Hard gelatin and HPMC involucres have different compositions therefore it is necessary to study the development of formulations involving these involucres as well as the evaluation of the final product quality. 711 0 obj
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The angle of repose determination was performed using the methodology proposed by Gil14 employing automated powder tester (Pharma Test PTG-2, Germany).
For the dissolution profiles were used five time points: 10, 15, 20, 30, 45 and 60 min, with subsequent replacement of the dissolution medium. 0000004650 00000 n
Kamel, S.; Ali, N.; Jahangir, K.; Shah, S. M.; El-Gendy, A. %PDF-1.4
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e-mail: 0000007354 00000 n
The high density found for the ampicillin (0.5557 g cm-3) provided the choice of capsule number 00 (0.95 mL). Gianotto, E. A. S.; Machado, H. T.; Miglioranza, B.; Fregonezi-Nery, M. M.; 3. 0000008089 00000 n
Keywords: ampicillin; gelatin; hydroxypropyl methylcellulose. Recebido em 23/1/11; aceito em 1/7/11; publicado na web em 9/8/11. 0000615305 00000 n
The choice of hydrophilic polymer in the matrix formulation can provide an appropriate combination of the swelling mechanisms, dissolution or erosion and determine the release kinetics in vitro.21 According to previous work,22 the drug incorporation in hydrophilic matrix systems is the most used method to prolong drug release dosage forms for oral use. 0000002661 00000 n
This study aims to develop and evaluate formulations containing ampicillin in capsules of gelatin and hydroxypropyl methylcellulose (HPMC). Furthermore, the f2 factor indicated the similarities between the dissolution profiles of the reference medicine and GEL-A (99.95%) and GEL-B (99.86%). 0000544877 00000 n
This trial was conducted in triplicate following the specific method described in the Brazilian Pharmacopoeia.16 Standard solution was used at a concentration of 1.25 mg mL-1. The determination of the granulometric strip was done mechanically using an agitator of sieves (Bertel, Brazil). The titration was performed with volumetric solution of 0.01 M sodium thiosulfate, and starch was used as indicator solution. However, there are no literature values for this drug granulometry. 0000017827 00000 n
, 0000020955 00000 n
0000003694 00000 n
For the statistical analysis of data obtained with the dissolution profiles, a comparative method was used between them and the efficiency of dissolution (ED%). 0000002468 00000 n
Because of the delay of the ampicillin release observed in the dissolution profiles, it becomes necessary to evaluate the drugs that can be conditioned in the HPMC capsules. 0000008943 00000 n
The excipients contained in the pharmaceutical dosage form were all of pharmaceutical grades and acquired from different distributors. The granulometry found in the test for the ampicillin was superior to 600 m. The assay values presented that ranged from 90.06 to 114.62% for HPMC-B and GEL-B, respectively. 0000413267 00000 n
After the method application, calculations were performed to determine the granulometric strip of the ampicillin.5. Furthermore, by having hygroscopic characteristics, ampicillin requires greater protection against humidity and the HPMC is a capsule with low humidity tenor when compared to the gelatin, which ensures the stability of drugs with this characteristic. patriciagomes0@yahoo.com.br, Curso de Farmcia, Centro Universitrio Franciscano, Rua dos Andradas, 1614, 97010-032 Santa Maria - RS, Brasil. 636 0 obj
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Other tested formulations showed significant differences (P <0.05, P <0.01 and P <0.001), which can be explained mainly by the difference in the nature of the involucres that directly influence the dissolution efficiency. The medicine reference Amplacilina (Eurofarma, Brazil) was also employed in this study. None presented linearity deviation. 0000622280 00000 n
0000535812 00000 n
(EN), Stay informed of issues for this journal through your RSS reader, Text Ku, M. S.; Li, W.; Dulin, W.; Donahue, F.; Cade, D.; Benameur, H.; Hutchison, K.; 8. 0000012048 00000 n
The samples were diluted to concentrations similar to the pattern. 0000614785 00000 n
0000534799 00000 n
Six units of each formulation were subjected to dissolution test and twelve to the dissolution profile. The results of this study suggest that differences exist between the hard gelatin and HPMC involucres used in the development of capsules containing ampicillin 500 mg, mainly in relation to disintegration, and dissolution tests. Bonfilio, R.; Mendona, T. F.; Pereira, G. R.; Arajo, M. B.; Tarley, C. R. T.; 18. In the case of the ampicillin, whose plasmatic pick is reached in 2 h, a concern is not observed regarding the use of the HPMC capsule for this drug. This may be related to the present excipients in the reference medicine (lactose, methylcellulose, stearic acid and magnesium stearate), which are different from the excipients used in the B formulation.