Relative bioavailability enhancement of simvastatin via dry emulsion systems: comparison of spray drying and fluid bed layering technology

Author(s):  
Mitja Pohlen ◽  
Jurij Aguiar Zdovc ◽  
Jurij Trontelj ◽  
Janez Mravljak ◽  
Mirjam Gosenca Matjaž ◽  
...  
Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1177
Author(s):  
Mitja Pohlen ◽  
Luka Pirker ◽  
Rok Dreu

The objective of this study was to explore the possible use of a new combination of two excipients, i.e., nanocrystalline cellulose (NCC) and macroporous silica (MS), as matrix materials for the compounding of dry emulsion systems and the effects these two excipients have on the characteristics of dry emulsion powders produced by the spray drying process. A previously developed liquid O/W nanoemulsion, comprised of simvastatin, 1-oleoyl-rac-glycerol, Miglyol 812 and Tween 20, was employed. In order to comprehend the effects that these two matrix formers have on the spray drying process and on dry emulsion powder characteristics, alone and in combination, a DoE (Design of Experiment) approach was used. The physicochemical properties of dry emulsion samples were characterised by atomic force microscopy, scanning electron microscopy, mercury intrusion porosimetry, energy-dispersive X-ray spectroscopy and laser diffraction analysis. Additionally, total release and dissolution experiments were performed to assess drug release from multiple formulations. It was found that the macroporous silica matrix drastically improved flow properties of dry emulsion powders; however, it partially trapped the oil—drug mixture inside the pores and hindered complete release. NCC showed its potential to reduce oil entrapment in MS, but because of its rod-shaped particles deposited on the MS surface, powder flowability was deteriorated.


Author(s):  
Sabitri Bindhani ◽  
Snehamayee Mohapatra

 Solid dispersion (SD) has been a major advanced technology in overcoming dissolution and bioavailability problem of poorly soluble compounds. Formulation of SD in water-soluble carrier has becoming more researched over the past four decades for solubility and relative bioavailability enhancement. By reduction of the size of the drug particle to the minimum level which will enhance drug wettability and ultimately bioavailability will be definitely improved. This review article elaborates recent advanced technology and characterization of SDs and also discusses the problems and their solution for the development of better formulations.


2021 ◽  
Author(s):  
Vishal Gurumukhi ◽  
Sanjaykumar Bari

Abstract Atazanavir (ATV) is widely used as anti-HIV agent with poor aqueous solubility which requires fabrication of novel drug delivery system to enhance therapeutic activity and safety. For this purpose, the quality by design (QbD) based ATV loaded nanostructured lipid carriers (NLCs) to address the challenges of bioavailability and its safety on oral administration. Herein, the main objective was to identify the influencing variables for the production of quality product. Considering this objective, quality target product profile (QTPP) was assigned and a systematic risk assessment study was performed to identify the critical material attributes (CMAs) and critical process parameter (CPP) having an influence on critical quality attributes (CQAs). Lipid concentrations, surfactant concentrations, and pressure of high-pressure homogenizer were identified as CMAs and CPP. ATV-NLCs were prepared by emulsification-high pressure homogenization method and further lyophilized to obtain solid-state NLCs. The effect of formulation variables (CMAs and CPP) on responses like particle size (Y1), polydispersity index (Y2), and zeta potential (Y3) was observed by central composite rotatable design (CCRD). The data were statistically evaluated by ANOVA for confirmation of a significant level (P<0.05). The optimal conditions of NLCs were obtained by generating design space and desirability value. The lyophilized ATV-NLCs were characterized by DSC, PXRD, and FT-IR analysis. The morphology of NLCs was revealed by TEM and FESEM. In vitro study suggested a sustained release pattern of drug (92.37±1.03 %) with a mechanism of Korsmeyer-Peppas model (r2 =0.925, and n=0.63). In vivo evaluation in Wistar rats showed significantly higher (p<0.001) plasma drug concentration of ATV-NLCs as compared to ATV-suspension using chylomicron flow block model. The relative bioavailability of ATV-NLCs was obtained to be 2.54 folds. Thus, a safe and promising drug targeting system was successfully developed to improve bioavailability and avoiding first-pass effect ensures to circumvent the acute-toxicity of liver.


Author(s):  
М. Б. Демчук ◽  
С. М. Гуреєва ◽  
Т. А. Грошовий

<p align="center"><strong>MODERN STATE OF CREATION, PRODUCTION AND RESEARCH OF DRUGS</strong></p><p align="center"><strong>M</strong><strong>.</strong><strong>B</strong><strong>. </strong><strong>Demchuk</strong><strong>, </strong><strong>S</strong><strong>.</strong><strong>M</strong><strong>. </strong><strong>Gureyeva</strong><strong><sup>1</sup></strong><strong>, </strong><strong>T</strong><strong>.</strong><strong>A</strong><strong>. </strong><strong>Hroshovyi</strong><strong></strong></p><p>TernopilStateMedicalUniversityby I.Ya. Horbachevsky</p><p><sup>1</sup>JSC “Farmak”</p><p><strong>Noti</strong><strong>ce</strong><strong> 19.</strong> The current state of development and research of multiple unit pellet systems.</p><p><strong>Summary: </strong>the literature on technological aspects of creations of pellets, features of compression pellet to obtain multiple unit pellet systems are summarized<strong>.</strong></p><p><strong>Keywords: </strong>pellets, methods of pellets, pellet pressing, multiple unit pellet systems.</p><p><strong>Introduction. </strong>Oral modified-release multiple-unit dosage forms have always been more effective therapeutic alternative to conventional or immediate release single-unit dosage forms. With regards to the final dosage form, the multiparticulates are usually formulated into single-unit dosage forms such as filling them into hard gelatin capsules or compressing them into tablets.</p><p>Pelletization is a technique that enables the formation of spherical beads or pellets with a mean diameter usually ranging from 0.5 to2.0 mm. These pellets can evantually be coated and very often used in controlled-release dosage forms. The use of pelletization and pellets leads to an improvement in the flowability, appearance and mixing properties, thus avoiding excessive dust and reducing segregation and, generally, eliminating undesirable properties and improving the physical or chemical properties of fine powders.</p><p>The pharmaceutical industry has developed a great interest in pelletization due to a variety of reasons:</p><p>– prevention of segregation of co-agglomerated components, resulting in an improvement of the uniformity of the content;</p><p>– prevention of dust formation;</p><p>– increasing bulk density and decreasing bulk volume;</p><p>– the defined shape and weight improves the appearance of the product;</p><p>– improvement of the handling properties, due to the free-flowing properties;</p><p>– improvement of the hardness and friability of pellets;</p><p>– controlled release application of pellets due to the ideal low surface area-to-volume ratio that provides an ideal shape for the application of film coatings.</p><p>Pellets are prepared by different techniques, such as extrusion and spheronisation, rotogranulation, solution, suspension or powder layering, spray-drying or spray-congealing.</p><p>Extrusion / spheronisation is a multistage process for obtaining pellets with uniform size from wet granulates (extrudates). The process is more labour-intensive and more expensive than the conventional wet-granulation technique, as its use should be limited only to the production of spherical pellets for controlled release of drugs.</p><p>The fluid-bed granulation consists in the spraying of a granulation solution onto the suspended particles, which then are dried rapidly in the hot air stream.</p><p>Rotogranulation is one of the most recent methods for the production of spheroids. The single-unit spheronizing system can be described using terms like centrifugal granulator, rotary fluidized-bed granulator, rotary fluid bed, rotary processor or rotor granulator.</p><p>Layering a suspension or a solution of a drug on a seed material (usually, a coarse crystal or nonpareil) can produce pellets that are uniform in size distribution and generally posess very good surphace morphology. These characteristics are especially desirable when pellets will be coated for the purpose of achieving a controlled release.</p><p>Dry powder layering is similar to the solution or suspension layering. Instead of these dispersions, the layering is performed using a drug powder.</p><p>Spray-drying represents another process with limited application in the development of pharmaceutical pelletized products, based on globulation. During spray-drying, a drug solution or suspension is sprayed, with or without excipients, into a hot-air stream, generating dry and highly spherical particles.</p><p>Spray-congealing (spray-chilling) is a technique similar to spray-drying. Spray-congealing is a process in which a drug is allowed to melt, disperse or dissolve in hot melts of gums, waxes, fatty acids or other melting solids. The dispersion is then sprayed into a stream of air and other gases with a temperature below the melting point of the formulation components.</p><p><strong>Conclusions.</strong> The basic requirements and approaches to development multiple unit pellet system, aspects and examples receipt of pellets and tablets based on them are described.</p>


2018 ◽  
Vol 10 (5) ◽  
pp. 105
Author(s):  
Nidhal K. Maraie ◽  
Yasser Q. Almajidi ◽  
Ahmed Alshadher

Objective: The aim of the work was to study the absolute and relative bioavailability (using rabbits) of ondansetron HCl (ONH)from our newly prepared intranasal mucoadhesive nanoemulsion in situ gel (NIG) in comparison to intranasal mucoadhesive in situ gel (IG) prepared by the conventional method and intravenous injection.Methods: Six male rabbits weighing 2.5-3 kg were used in this study, where the dose of ondansetron HCl (ONH) was calculated based on the body surface area (BSA) which is equivalent to 140μl (containing 10 mg/ml) of NIG and IG and 700μl of intravenous Zofran® injection (containing 2 mg/ml) were given to the rabbits, separated with one week washout period. Serial blood samples were withdrawn and analyzed for simultaneous determination of the drug using HPLC (Knaure; 150 ×4.6 mm; 5 μm particle size; 25 cm length) supported by guard column C18-4 mm diameter.Results: The pharmacokinetics parameters for NIG; Cmax, Tmax, AUC0-t, AUC0-∞were found to be greater than conventional in situ gel (IG). In vivo pharmacokinetic studies in rabbits showed a significant increase in Cmax and AUC 0-α(P<0.001) with shorter Tmaxusing NIG compared to IG containing the same NIG excipients, while the absolute bioavailability for NIG and IG (was 80.541 and 51.068 respectively).Conclusion: The present studies ratify the bioavailability enhancement potential of NE used to prepare NIG for the drug and significantly high absolute bioavailability to be used as a successful alternative route to the IV injection and improve patient compliance.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1063
Author(s):  
Yingxi Zhang ◽  
Yuan Gao ◽  
Xiaoxiao Du ◽  
Rou Guan ◽  
Zhonggui He ◽  
...  

It is crucial to improve poorly water-soluble orally administered drugs through both preclinical and therapeutic drug discovery. A co-amorphous formulation consisting of two low molecular weight (MW) molecules offers a solubility/dissolubility advantage over its crystalline form by maintaining their amorphous status. Here, we report on a co-amorphous solid dispersion (SD) system that includes inert carriers (lactose monohydrate or microcrystalline cellulose) and co-amorphous sacubitril (SAC)-valsartan (VAL) using the spray drying process. The strong molecular interactions between drugs were the driving force for forming robust co-amorphous SDs. Our system provided the highest solubility with more than ~11.5- and 3.12-times solubility increases when compared with the physical mixtures. Co-amorphous lactose monohydrate (LM) SDs showed better bioavailability of APIs (~356.27.8% and 154.01% for the relative bioavailability of LBQ 657 and valsartan, respectively). Co-amorphous inert carrier SDs possessed an excellent compressibility for the production of a direct compression pharmaceutical product. In conclusion, these brand-new co-amorphous SDs could reduce the number of unit processes to produce a final pharmaceutical product for downstream manufacturability.


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