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Background: The fact that about 90 % of newly discovered API’s or new molecular entity(NME) have little or no aqueous solubility, causes a significant protest to the initialization of development and their scale up of dosage form in the Pharma Industry. Aqueous solubility of API’s has critical role in drug dissolution or availability of drug at the site of action or bioavailability, when a dosage form is administered orally.Objective: The object of this study is to formulate a modified release tablet dosage form of a poorly aqueous soluble drug, which not only have higher aqueous solubility or bioavailability but also have sustained release characteristics with high mechanical strength &their commercial viability. Numerous techniques are available for the solubility enhancement but all individual techniques have its own limitations for commercialization.Method: Aqueous solubility of drugs is improved by the known Solubility enhancement techniques like Micronization &Solid dispersions. After successful solubility enhancement, sustained release or modified release tablets of poorly aqueous soluble drug can be easily formulated into a suitable shape or size by using a known Polymer Matrix Sintering Technology with commercial feasibility. Micronization of poorly water-soluble drugs can be performed by Air Jet Mill or Ball Mill. Whereas Solid dispersion technique involves, molecular dispersion of poorly soluble drug in a suitable inert carrier, to form an amorphous and highly soluble compounds. Sintering Technology is defined as the bonding of adjacent particle surfaces in a mass of powder, or in compact, by the application of heat. Conventional sintering technique involves the heating of compact at a temperature below the melting point of the solid constituents in a controlled environment under atmospheric pressure.Results: Enhanced solubility of poorly soluble API’s by these proposed techniques is due to either conversion of crystalline compound in to amorphous form or reduction of particle size to its molecular level by the application of Micronization or solid dispersion techniques. The developed modified release tablets will show a sustained release characteristic due to Sintering aspect and provides enhanced solubility of BCS class II or IV drugs.Conclusion: Novel modified release tablets have been designed through consolidation of Solubility enhancement and Polymer Matrix Sintering technologies. Simultaneous exploitation of well-known and established approaches- Micronization (optimum particle size reduction) or solid dispersion, optional surfactant and Polymer Matrix Sintering Technique in the recent concept, produces significant enhancement of solubility of poorly water soluble API’s without compromising the content uniformity of dosage form and also provide a modified or sustained release characteristics with high mechanical strength. The release profile of drug can be easily tailored by using combination of both techniques where challenges of low solubility are prominent.
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OBJECTIVE:To screen the optimal micronization technology of Alitretinoin crude drug. METHODS:Using characteristic value of particle size distribution [d(0.9)] and the content of impurity A of crude drug after crushed as indexes, crushing method(universal pulverizer,ball crusher,airslide disintegrating mill),crushing gas source(compressed air,high pressure nitrogen)and crushing pressure(0.2,0.4,0.6 MPa)of Alitretinoin crude drug were screened,and validation test was also conducted. RESULTS:The optimal technology was as follows as airslide disintegrating mill,high pressure nitrogen as gas source,at 0.4 MPa.In validation test,particle sizes for 3 batches of crude drug after crushed were 8.57,8.55,8.54 μm(<10 μm, RSD=0.15%,n=3). The content of impurity A was not increased compared with before crushed(0.07%). CONCLUSIONS:Screened micronization technology of Alitretinoin crude drug is feasible and stable in quality.
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Objective To prepare micronized nimodipine push-pull osmotic pump (PPOP) controlled release tablets . Methods The nimodipine as a model drug ,micronization technique was applied to the PPOP method .Designed and prepared the controlled release of the nimodipine tablet for 12 hours in vitro .The factor f2 was used to evaluate the similarities of differ-ent dissolution profiles ,and the optimal formulation was performed .Results The micronized nimodipine PPOP controlled re-lease tablets were successfully prepared with excellent zero-order release characteristics .The PPOP tablet′s release behavior was close to the zero-order release equation (r= 0 .998 4) .Conclusions The controlled-release formulation was prepared suc-cessfully .Micronized technique combined with the PPOP method significantly increased the release of the nimodipine tablet , the poorly soluble drug ,in vitro .
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Objective: Camptothecin (CPT) as a kind of poorly soluble drug was conducted micronization research. Methods: CPT micronized powder was prepared by emulsification method using emulsification machine and high pressure homogenizer. Moreover, single factor method was utilized to optimize. Dissolution and oral bioavailability study on CPT micronized powder prepared under the best emulsification conditions was conducted. Results: The best preparation conditions were as follows: The dosage of Tween-80 as the surfactant was 0.4%; The concentration of CPT in chloroform-methanol (8:2) mixed solution was 1 mg/mL; The volume ratio of water-organic phase was 7:3; The homogenate speed was 7 000 r/min for 11 min. The particle size of CPT micronized powder prepared under the optimized conditions was (165.6 ± 5.3) nm. The scanning electron microscopy (SEM) results showed that CPT micronized powder presented regular strip shape and uniform particle size. The dissolution study indicated that the solubility and dissolution rate of CPT micronized powder was increased by 1.36 and 4.09 times compared with the raw CPT powder. The results of oral bioavailability showed that compared with the raw CPT powder, the relative bioavailability of CPT micronized powder in mice was increased by 2.10 times. The results of gas chromatography showed that residual solvents in CPT micronized powder accorded with the standard of ICH. Conclusion: Solubility and dissolution rate of CPT are both improved since CPT micronized powder is prepared by emulsification method. So the oral bioavailability is also improved.
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In recent years, pulmonary drug delivery as an attractive non-invasive administration way has been gaining intensive attention. The market for inhalable therapy has constantly grown over past years. Various particle engineering techniques have been employed to exploit the drug particles or drug-loaded particles used for pulmonary delivery with suitable physical properties. Those tailor-made inhalable particles offer the possibility of efficient delivering to lungs and the most optimal therapeutic outcomes. This review highlights the deposition mechanism of particles in lungs and several particle engineering techniques for pulmonary drug delivery, in particular two novel techniques PulmoSphere™ and TechnoSphere™, which have been used in the marketed products.
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In recent years,pulmonary drug delivery as an attractive non-invasive administration way has been gaining inten?sive attention. The market for inhalable therapy has constantly grown over past years. Various particle engineering techniques have been employed to exploit the drug particles or drug-loaded particles used for pulmonary delivery with suitable physical properties. Those tailor-made inhalable particles offer the possibility of efficient delivering to lungs and the most optimal therapeutic outcomes. This review highlights the deposition mechanism of particles in lungs and several particle engineering techniques for pulmonary drug delivery,in particular two novel techniques PulmoSphereTM and TechnoSphereTM,which have been used in the marketed products.
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Aflatoxins, fumonisins and zearalenone take part of the most studied mycotoxin groups due to their toxic effects on animal and human health. This research evaluated samples of soybeans meal used in animal food industry. A hundred and twenty one soybean meal samples were analyzed, so that 66 were analyzed before the industrial processing of micronization and 55 after it. The bromatological average of samples before micronization showed the following answers: 12.4% moisture; 46.4% protein; 79.5% protein solubility; 5.9% ash content; 2.2% fat; 4.3% fiber and 0.02 (ΔpH) of urease activity. The samples of micronization soybean meal showed 7.0% average values for moisture and 48.6% for crude protein. The mycotoxin levels were low in natura soybean meal; therefore, average values were 0.5μg kg-1, 29.6μg kg-1 and 56.8μg kg-1 for aflatoxin, zearelenone and fumonisin, respectively. After micronization, the average values for the studied samples were 1.3μg kg-1, 67.5μg kg-1 and 89.1μg kg-1, respectively for the same mycotoxins. The results for bromatological and mycotoxin analyses indicate similarity with the established patterns according to the Brazilian Compendium for Animal feed and reference literature. However, at least one of the three studied mycotoxin was detected in all of the analyzed samples and there was greater contamination of soybeans meal after the micronization process.
Aflatoxinas, fumonisinas e zearalenona pertencem aos grupos de micotoxinas mais estudados, devido aos efeitos tóxicos provocados na saúde animal e humana. O presente estudo avaliou amostras de farelo de soja utilizado em uma indústria de nutrição animal. Foram analisadas 121 amostras de farelo de soja, sendo 66 antes do processo industrial de micronização e 55 após o processamento. A composição bromatológica média das amostras antes da micronização apresentou 12,4% de umidade; 46,4% de proteína; 79,5% de solubilidade proteica; 5,9% de cinzas; 2,2% de gordura; 4,3% de fibra e 0,02 (ΔpH) de atividade ureásica. As amostras de farelo de soja micronizado apresentaram valores médios de 7.0% para umidade e 48,6% para proteína bruta. Os resultados apresentaram baixos níveis de micotoxinas no farelo de soja "in natura", detectando valores médios para aflatoxina, zearalenona e fumonisina de 0,5μg kg-1, 29,6μg kg-1e 56,8μg kg-1, respectivamente. Após a micronização, as amostras apresentaram valores médios de 1,3μg kg-1, 67,5μg kg-1 e 89,1μg kg-1, respectivamente, para as mesmas micotoxinas. Os resultados das análises bromatológicas e de micotoxinas evidenciaram conformidade com os padrões estabelecidos pelo Compêndio Brasileiro de Alimentação Animal e literatura de referência. Entretanto, detectou-se a presença de, no mínimo, uma das três micotoxinas pesquisadas em todas as amostras analisadas e uma maior contaminação no farelo de soja após o processo de micronização.
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The purpose of this study was to produce of microparticles for Dry Powder Inhalation, produced by environmentally driven In-situ Microcronization technique at different processing parameters, for inhalation therapy. Typically particle size reduction process employs jet-milling technology which can be destructive to the solid-state properties of the particles. Salbutamol Sulphate, as one of the β2-adrenoceptor stimulant commonly used in the treatment of bronchial asthmaby pulmonary delivery.The objective of the current work was to developed microcrystals by using In-situ Microcronization technique with different processing parameters. A response surface type central composite design were employed using Design-Expert 5.0 software (Stat Ease, QD Consulting, Penzance, UK) with the factors investigated werestirrer speeds investigated were 500(-1), 1000(0) and 1500 (1) rpm, addition rate of non-solvent i.e ethanol was studied at 50(-1), 100(0) and 150(1) g /min and stabilizer conc. were 0.5(-1), 1(0) and 1.5 %( 1). In the bottom up technique of micro sizing we use in-situmicronization technique which carried out using the solvent change method in presence of HPMC as stabilizing agent. The suspension wasspray dried thereafter.Optimize the process variables for less mean particle size and high Fine Particle Fraction (FPF). Spray dried crystals were subjected to XRD, FTIR, DSC and SEM analysis for stability. The PSD and FPF also depended on the balance of meso and micromixing determined by the crystallization conditions. Optimized formulation was identified and characterized to determine their suitability for pulmonary delivery by using MSLI. Optimized formulation showed the highest FPF loaded and FPF emitted of 78 (1%) and 84 ( 3%) respectively, depositing mainly on stages 3 and 4, with much lower amounts collected on the higher stages of the MSLI.
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Amoxicillin, a well-known antibiotic, has a broad spectrum against gram-negative and gram-positive bacteria. This experiment was conducted in order to investigate the effect of micronized and non-micronized amoxicillin prepared using different comminution techniques on change in blood concentration of rats. Forty adult male Sprague Dawley rats (6~7 weeks of age, body weight 128.3 +/- 10.7 g) were randomly allocated to two treatment groups: micronized amoxicillin (MA) group treated with micronized amoxicillin trihydrate powder (particle size, over 90% of 10 microm), non-micronized amoxicillin (NMA) group treated with non-micronized amoxicillin trihydrate powder (particle size, over 70% of 100 microm), given 480 mg/kg body weight once daily for four days. The results showed a significant increase in serum concentration in the MA group on days 3 and 4, compared to the NMA group (P<0.05). In particular, serum concentration of the MA group on day 4 was increased almost two times that of the NMA group. The results indicate that due to the increase of the drug's oral bioavailability, higher serum concentration would be achieved with the micronized amoxicillin trihydrate than with the non-micronized drug.
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Adult , Animals , Humans , Male , Rats , Administration, Oral , Amoxicillin , Biological Availability , Body Weight , Gram-Positive Bacteria , Rats, Sprague-DawleyABSTRACT
AIM: The powder characteristic, water and ethanol extraction amount, extraction amount of active ingredient ferulic acid were comparatively studied between crude powder and micronized powder to explore the application of micronization technology to Angelica Sinennsis. METHODS: Angelica Sinennsis powder was characterized by laser diffraction analyzer and scanning electron microscopy, the angle of repose and bulk density were measured, the water and ethanol extraction were quantified by cooled and heated extraction, the active ingredient ferulic acid was detected by RP HPLC after it released from Angelica Sinennsis. RESULTS: The differences of particle characteristic and surface morphology between the crude and superfine powder were significant, however, water and enthanol extraction amount were not increased markedlky, the dissolution amount of ferulic acid was almost the same. CONCLUSION: Pharmaceutical characteristic of Angelica Sinennsis powder is affected by micronization, but its bioavailability is not improved. Micronization technology is not suitable to Angelica Sinennsis.