Karakterisasi Sifat Fisik Granul Dengan Bahan Pengikat Amylum Manihot Pragelatinasi Dan Polivinilpirolidon

Granules come from small particles which then become single larger particles to form a lump. The binder in the granules is used to ensure the incorporation of the powder particles in the granules. Manihot starch is a natural binder and polyvinylpyrrolidone is a synthetic binder, because manihot starch has poor flow properties, it is necessary to modify it by pregelatination. The purpose of this study was to determinethe characterization of the physycal properties of granules with a natural binder of pregelatinized starch manihot and and synthetic polyvinylpyrrolidone on the physical properties of the granules. Variations in the concentration of pregelatinated starch manihot were 3% and 5% respectively. The granulation process is carried out by mixing all materials that have easy flowing properties. The resulting granules were evaluated for their physical properties and then the data were analyzed using SPSS with the One Way ANOVA method with a 95% confidence level. The results of the organoleptic test are white granules but on F1 and F2 there are brown spots then round shape and characteristic odor, the flow time meets the requirements of 10 g/second, the angle of repose test meets the requirements <30˚, compressibility meets the requirements <15%. The results of statistical analysis showed a significant difference (sig <0,05) in the flow time test. The optimum concentration of pregelatiansi manihot starch is 5% (F2) and polyvinylpyrrolidone 5% (F4). The Suggest for further researchers can use other natural excipients and make modifications to improve the physical characteristics of the granules. Keyword: Amylum Manihot; granules;polivinilpirolidon; pragelatination AbstrakGranul berasal dari partikel-partikel yang berukuran kecil kemudiam menjadi partikel tunggal yang lebih besar membentuk suatu gumpalan. Bahan pengikat pada granul digunakan untuk menjamin penyatuan partikel serbuk dalam granul. Amilum manihot merupakan pengikat bahan alami dan polivinilpirolidon merupakan pengikat bahan sintetis, dikarenakan amilum manihot memiliki sifat alir yang kurang baik maka perlu dilakukan modifikasi dengan pragelatinasi. Tujuan dari penelitian ini untuk mengetahui karakterisasi sifat fisik granul dengan bahan pengikat alami amilum manihotpragelatinasi dan bahan sintetis polivinilpirolidon. Variasi konsentrasi bahan pengikat masing-masing adalah 3% dan 5%. Proses granulasi dilakukan dengan mencampurkan seluruh bahan yang memiliki sifat mudah mengalir. Granul yang dihasilkan di evaluasi sifat fisiknya kemudian data dianalisis menggunakan SPSS dengan metode One Way ANOVA dengan tingkat kepercayaan 95%. Hasil uji organoleptisgranulbewarna putih namun pada F1 dan F2 terdapat bintik coklat kemudian bentuk bulat dan bau khas, waktu alir memenuhi syarat ≤10 g/detik, uji sudut diam memenuhi syarat <30˚, kompresibilitas memenuhi syarat <15%. Hasil analisis statistik terdapat perbedaan bermakna (sig < 0,05) pada uji waktu alir.Konsentrasi optimum bahan pengikat amylummanihotpragelatiansi 5% (F2) dan polivinilpirolidon 5% (F4). Saran untuk peneliti selanjutnya dapat digunakan bahan eksipien alami yang lainnya dan dilakukan modifikasi untuk meningkatkan karakteristik sifat fisik granul. Kata kunci: Amilum Manihot; granul;polivinilpirolidon; pragelatinasi

Study of the quantitative factors influence on pharmaco-technological properties of powder masses and tablets with plant extracts and essential oil

The available range of phytopreparations for topical use in the oral cavity does not fully meet the needs of patients as mainly medicinal plant raw materials and tinctures of domestic production represent it. Therefore, we developed a pharmaceutical composition in the form of tablets based on dry extracts herb of Geranium sanguineum L., Geranium sibiricum L. and essential oil of Salvia sclare. To optimize the composition of the tablets it is necessary to study and select the necessary excipients and their quantities, which was the purpose of the work. In order to study the influence of 10 quantitative factors on the properties of powder masses and the main quality indicators of tablets with plant extracts and essential oil, the method of random balance was used. The obtained powder mixtures and tablets based on them were subjected to the determination of the following pharmaco-technological parameters: bulk density, tapped density, flowability, the angle of repose, the uniformity of weight, tablet hardness testing, the friability test, disintegration time, desirability function. The pharmaco-technological index of bulk density improves with an increase in the amount of Pregelatinized Starch, Mannitol 60, Emcompress, as well as a decrease in the amount of Neusilin UFL2 and Neusilin US2. Regarding the tapped density, Neusilin US2 significantly affects it, with the increase of which this indicator decreases. With the introduction of more Neusilin US2, Mannitol 60, Pregelatinized Starch, Ludipress, Emcompress and Magnesium Stearate, the value of the angle of repose is improved. The average mass has the greatest influence on fluidity, at its decrease this indicator improves. The same happens with the introduction of Neusilin UFL2, Neusilin US2, Pregelatinized Starch and Magnesium Stearate. The uniformity of weight of all series of tablets fluctuates within ± 5%, and friability to 1%, which meets the requirements of the State Pharmacopoeia of Ukraine. Also, despite the results obtained, all series of tablets were very strong, with the lowest tablet hardness testing – 159 N. The disintegration of the tablets varies within 6 minutes. After evaluating the results of the scattering diagrams of all pharmaco-technological parameters as well as the desirability function, Neusilin US2, МCC 102, Sodium croscarmellose, Mannitol 60 and Magnesium Stearate were selected for further research. The average weight of tablets should be increased to 0.55 g.

Application of data-intelligence algorithms for modeling the compaction performance of new pharmaceutical excipients

Background Pharmaceutical excipient development is an extensive process requiring a series of pre-formulation studies to evaluate their performance. The present study compares the conventional compaction and compression pre-formulation studies with artificial intelligence (AI) modeling to predict the performances of thermally and chemically modified starches obtained from Livingstone potato. Results The native starch was modified by three methods, and we obtained the following starches; pregelatinized starch (PS), ethanol dehydrated pregelatinized starch (ES), and acid hydrolyzed starch (AS). Microcrystalline cellulose (Avicel® PH101) was employed as a reference since its use in tablet direct compression has been established. The role of compaction pressure on the degree of volume reduction of the tablets was studied using Kawakita and Heckel models which highlighted that when the starch is modified by pregelatinization followed by ethanol dehydration, and/and or acid hydrolysis modification, a directly compressible starch can be obtained that can plastically deform. The data-intelligence results indicated the reliability of the AI-based models over the linear models. Hence, the comparative results demonstrated that the Adaptive neuro-fuzzy inference system (ANFIS) outperformed the other two models in modeling the performance of all of the four excipients with considerable performance accuracy. Conclusion The compressibility indices have shown matching characteristics of AS and ES to Avicel® PH101 in terms of direct compressibility potential than PS. Moreover, the data intelligence modeling demonstrates the reliability and satisfactory of ANFIS as a hybrid model over the other two models with increased performance skills in modeling the compaction properties of these novel pharmaceutical excipients.

Pregelatinized Starch: Variability in Gelatinization and its Influence on Product Performance

Starch and its derivatives are one of the significant excipients used in the pharmaceutical formulations due to their multi-purpose functionalities. The purpose of this study is two-fold: (1) Firstly, to propose a systematic approach in understanding the material properties of a starch derivative (pregelatinised starch/PGS) using analytical ‘toolbox’ as part of ‘alternative supplier sourcing’, and secondly (2) To demonstrate the effect of PGS from different vendors on the tablet disintegration using model formulations. Contextually, a two-tier characterisation procedure is generally considered as a prerequisite for establishing the sameness of the material obtained either from different batches or from various vendors. Primarily, the sameness between typical quality-control tests and compendial requirements are to be established. If similar, then sameness between the functional characteristics is to be established. In this context, the PGS from two vendors met the specifications, and there were no differences for the test results in the certificates of analysis. However, when subjected to functionality assessment, the two lots were found to be distinctly different. The influence of the functional property variations was further exemplified from viscosity results of raw material. Furthermore, this difference was even more evident when the model formulations were subjected to disintegration testing. The similarity in compendial tests but significant differences in functionality characteristics for the PGS of two vendors can be unravelled by considering variations in particle size, crystallinity, starch retrogradation and these changes are potentially attributed to the differences in the gelatinisation procedures adopted by the vendors.

Demonstration of Advanced Data Mining Tools for optimization of Pellets employing Modified Extrusion-Pelletization Technique

Background: The multi particulate drug delivery system is preferred due to its numerous advantages but the batch to batch consistency and to achieve desired physical properties are the major challenges in the formulation of such dosage form. Objective: The objective of the present study was to explore the concept of quality by design for the development of galantamine HBr controlled release pellets using a modified palletization technique. Methods: Compritol 888 and Ethocel were chosen as hydrophobic release retardants while Avicel was chosen as pelletization aid. A compatibility study was conducted between the drug and excipients. Drug loaded extrudes were prepared by using a mixture of isopropyl alcohol, and dichloromethane. Before converting the wet extrudes in pellets, pregelatinized starch was sprinkled on them to improve the physical properties of the pellets. The pellets were characterized for size, shape, and flow. The critical evaluation parameter was the drug dissolution pattern in distilled water. The dissolution data were treated with advanced data mining techniques. The in-vivo profile was predicted employing pharmacokinetic parameters of the drug and in-vitro drug release data of optimized batch pellets. Results: The failure mode and effect analysis revealed that the amount of Compritol 888 ATO and Ethocel were the most critical formulation parameters. The results of FTIR and DSC revealed compatibility between the drug and the excipients. The spherical pellets exhibited good flow. The drug dissolution studies of the batches, prepared according to the central composite design, revealed modified drug release. Multiple regression analysis and analysis of variance were performed to identify statistically significant factors. Contour plots demonstrated the impact of the amount of Compritol 888 and ethyl cellulose. The Design-Expert software was used to identify optimized formulation. The predicted in-vivo plasma concentration-time profile revealed the modified drug release up to 12h. Conclusions: Compritol and Ethocel were able to retard the drug release up to 12 hrs in distilled water. The innovative finding of this study is the use of a dry binder (pregelatinized starch) to improve the characteristics of pellets. Other dry binders are expected to show a similar effect. The newer processing technique can be of use in the industry.