scholarly journals Lyophilization-free proliposomes for sustained release oral delivery of hydrophobic drug (cinnarazine): a comparative study

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Omar S. Abu Abed ◽  
Srilikha Mulkala ◽  
Israa Sharif ◽  
Asma M. Abdin ◽  
Amal A. Alkordy
Keyword(s):  
Oral Delivery ◽  
Encapsulation Efficiency ◽  
Storage Period ◽  
Gastric Fluid ◽  
Dissolution Experiment ◽  
Pharmacokinetic Properties ◽  
Poorly Soluble ◽  
Successful Approach ◽  
Crystalline Nature ◽  
Stability Issues

Abstract Objectives Cinnarizine is used for the treatment of vestibular disorders. However, its poor solubility limits its clinical uses due to many challenges. Liposomes were utilised to improve the release profile of many poorly soluble drugs. However, liposomes face many stability challenges during the storage period. This study aims to develop proliposomes designed for the oral delivery of cinnarizine with enhanced stability characteristics. Methods Three cinnarizine entrapping Proliposomal formulations were prepared with different ingredients and compared with their liposomal counterparts. Both vesicular approaches were characterised for their particle size, encapsulation efficiency, drug release and stability. Results The proliposomes were superior to liposomes in their stability and release profiles. Although no significant changes were noticed between the encapsulation efficiency percentage of the liposomal and proliposomal formulations on the day of preparation, storing the formulations for two weeks ended up with significant leakage of the drug from liposomes (p < 0.05) due to stability issues, but not in proliposomes. Moreover, the proliposomes released 100% of cinnarizine throughout the dissolution experiment in gastric fluid in comparison with the total released drug of 70% from the liposomes. Conclusions Proliposomes provided a successful approach to deliver lipophilic drugs orally to improve their pharmacokinetic properties by converting their crystalline nature into more amorphous agents.

Approaching stability challenges for flow cytometry in a regulated bioanalytical environment

Bioanalysis ◽  
2019 ◽  
Vol 11 (20) ◽  
pp. 1845-1858 ◽  
Author(s):  
Anamica Muruganandham ◽  
Carolyne Dumont ◽  
Kuiyi Xing
Keyword(s):  
Flow Cytometry ◽  
Critical Parameter ◽  
Storage Period ◽  
Reliable Data ◽  
Clinical Samples ◽  
Sample Collection ◽  
Testing Laboratory ◽  
Stability Parameters ◽  
Stability Issues ◽  
Limited Period

Stability of samples for flow cytometry is a critical parameter since storage period of samples is restricted to only a limited period after collection. For most studies, clinical samples have to be shipped to a testing laboratory, in contrast to preclinical samples, which can be analyzed on-site or off-site. Therefore, evaluating stability is critical to provide flexibility on testing of samples to obtain reliable data. A wide variety of factors contributes to establishing stability from sample collection through acquisition. We provided suggestions for experimental and stability parameters to be taken into consideration when designing a flow cytometry method. The case studies presented represent how certain stability issues were overcome to perform flow cytometry assays in a regulated bioanalytical environment.

scholarly journals Relative Contributions of Solubility and Mobility to the Stability of Amorphous Solid Dispersions of Poorly Soluble Drugs: A Molecular Dynamics Simulation Study

Pharmaceutics ◽  
2018 ◽  
Vol 10 (3) ◽  
pp. 101 ◽  
Author(s):  
Michael Brunsteiner ◽  
Johannes Khinast ◽  
Amrit Paudel
Keyword(s):  
Molecular Dynamics ◽  
Oral Delivery ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Dynamics Simulation ◽  
Limiting Factor ◽  
Poorly Soluble Drugs ◽  
Formulation Development ◽  
Amorphous Solid Dispersions ◽  
Poorly Soluble

Amorphous solid dispersions are considered a promising formulation strategy for the oral delivery of poorly soluble drugs. The limiting factor for the applicability of this approach is the physical (in)stability of the amorphous phase in solid samples. Minimizing the risk of reduced shelf life for a new drug by establishing a suitable excipient/polymer-type from first principles would be desirable to accelerate formulation development. Here, we perform Molecular Dynamics simulations to determine properties of blends of eight different polymer–small molecule drug combinations for which stability data are available from a consistent set of literature data. We calculate thermodynamic factors (mixing energies) as well as mobilities (diffusion rates and roto-vibrational fluctuations). We find that either of the two factors, mobility and energetics, can determine the relative stability of the amorphous form for a given drug. Which factor is rate limiting depends on physico-chemical properties of the drug and the excipients/polymers. The methods outlined here can be readily employed for an in silico pre-screening of different excipients for a given drug to establish a qualitative ranking of the expected relative stabilities, thereby accelerating and streamlining formulation development.

scholarly journals High-Throughput Excipient Discovery Enables Oral Delivery of Poorly Soluble Pharmaceuticals

2016 ◽  
Vol 2 (10) ◽  
pp. 748-755 ◽  
Author(s):  
Jeffrey M. Ting ◽  
Swapnil Tale ◽  
Anatolii A. Purchel ◽  
Seamus D. Jones ◽  
Lakmini Widanapathirana ◽  
...  
Keyword(s):  
High Throughput ◽  
Oral Delivery ◽  
Poorly Soluble

scholarly journals Design of insulin-loaded alginate nanoparticles: Influence of the calcium ion on polymer gel matrix properties

2006 ◽  
Vol 12 (1) ◽  
pp. 47-52 ◽  
Author(s):  
Catarina Reis ◽  
R.J. Neufeld ◽  
António Ribeiro ◽  
Francisco Veiga
Keyword(s):  
Particle Size ◽  
Calcium Ions ◽  
Oral Delivery ◽  
Encapsulation Efficiency ◽  
Particle Production ◽  
Calcium Salt ◽  
Mass Relation ◽  
Polymer Gel ◽  
Oil Emulsion ◽  
Water In Oil Emulsion

Alginate-based nanoparticles were produced by dispersing alginate aqueous solution containing an insoluble calcium salt within mineral oil forming a water-in-oil emulsion. Subsequently, alginate gelled upon contact with the calcium ions due to the physical cross-linking between the carboxylate anions of the alginate and the calcium ions. The influence of the calcium salt, added in varying amounts, on gel integrity and on particle size was investigated. The efficiency of encapsulating active biological compounds by nanoparticles was also assayed. The calcium concentration was seen to be a crucial parameter in particle production, influencing the particle size, the viscosity of the solutions at different stages of the emulsification/gelation process and, finally, the encapsulation efficiency. The most appropriate mass relation between calcium and alginate was 7% (w/w). Under this condition, the smallest mean diameter obtained was 2.604 ? 2.141 ?m combined with the narrowest range of particle sizes. The encapsulation efficiency of insulin was over 71 %. These previous characteristics appear to be best suited for producing small, well-dispersed and stable nanoparticles with high encapsulation of insulin. This particulate system may be considered as a promising carrier for the oral delivery of insulin.

Tocol modified glycol chitosan for the oral delivery of poorly soluble drugs

2012 ◽  
Vol 423 (2) ◽  
pp. 452-460 ◽  
Author(s):  
Nicolas Duhem ◽  
Julien Rolland ◽  
Raphaël Riva ◽  
Pierre Guillet ◽  
Jean-Marc Schumers ◽  
...  
Keyword(s):  
Oral Delivery ◽  
Poorly Soluble Drugs ◽  
Glycol Chitosan ◽  
Poorly Soluble

Oxidized Mesoporous Silicon Microparticles for Improved Oral Delivery of Poorly Soluble Drugs

2009 ◽  
Vol 7 (1) ◽  
pp. 227-236 ◽  
Author(s):  
Feng Wang ◽  
He Hui ◽  
Timothy J. Barnes ◽  
Christian Barnett ◽  
Clive A. Prestidge
Keyword(s):  
Oral Delivery ◽  
Poorly Soluble Drugs ◽  
Mesoporous Silicon ◽  
Poorly Soluble

scholarly journals Heightening the solubility of poorly soluble fenofibrate by Solid Dispersion Technique

2020 ◽  
Vol 11 (1) ◽  
pp. 663-668
Author(s):  
Yasmin Begum M ◽  
Prathyusha Reddy G
Keyword(s):  
Dissolution Rate ◽  
Solid Dispersion ◽  
Aqueous Solubility ◽  
Gastric Fluid ◽  
Lipid Lowering ◽  
Solid Inclusion ◽  
Gastrointestinal Fluid ◽  
Poorly Soluble ◽  
Dispersion Technique ◽  
Lowering Drug

The intention of the current study was to boost the solubility of Fenofibrate by solid dispersion technique which is an efficient technique in improving the solubility and hence the dissolution rate of poorly soluble drugs in the form of eutectic mixtures by producing fine dispersion when in contact with gastrointestinal fluid and also the technique offers the choices of carriers to be combined with drug conveniently to improve the solubility to a considerable extent. Fenofibrate a BCS class II Antihyperlipidemic drug belongs to fibrate class and it is a lipid-lowering drug used in the treatment of hyperlipidemia. Fenofibrate is insoluble in water and hence shows poor dissolution in gastric fluid with reduced absorption characteristics. In order to improve the solubility, dissolution rate, gastrointestinal absorption and oral bioavailability, it was decided to prepare fenofibrate solid dispersion and evaluated. They were prepared using poly ethylene glycol 4000, 6000, 8000 and β-cyclodextrin by fusion technique and optimized solid dispersion was also lyophilized. Physical characterization of solid inclusion complex of fenofibrate was studied and showed that there were no drug excipients interactions. Dissolution studies showed a momentous rise in a dissolution of Fenofibrate when dispersed in polymers. Inturn aqueous solubility was enlarged linearly as a function of the concentration of β- Cyclodextrin.

scholarly journals In Vitro Evaluation of Eudragit Matrices for Oral Delivery of BCG Vaccine to Animals

2019 ◽  
Author(s):  
Imran Saleem ◽  
Allan Coombes ◽  
Mark Chambers
Keyword(s):  
Oral Delivery ◽  
Freeze Drying ◽  
Tween 80 ◽  
Gastric Fluid ◽  
Powder Compaction ◽  
Bcg Vaccine ◽  
Simulated Gastric Fluid ◽  
Physical Damage ◽  
Freeze Dried

Bacillus Calmette-Gu&eacute;rin (BCG) vaccine is the only licensed vaccine against tuberculosis (TB) in humans and animals. It is most commonly administered parenterally but oral delivery is highly advantageous for immunisation of cattle and wildlife hosts of TB in particular. Since BCG is susceptible to inactivation in the gut, vaccine formulations were prepared from suspensions of Eudragit L100 copolymer powder and BCG in PBS, containing Tween 80, with and without the addition of mannitol or trehalose. Samples were frozen at -20oC, freeze-dried and the lyophilised powders were compressed to produce BCG-Eudragit matrices. Production of the dried powders resulted in a reduction in BCG viability. Substantial losses in viability occurred at the initial formulation stage and at the stage of powder compaction. Data indicated that the Eudragit matrix protected BCG against simulated gastric fluid (SGF). The matrices remained intact in SGF and dissolved completely in SIF within three hours. The inclusion of mannitol or trehalose in the matrix provided additional protection to BCG during freeze-drying. Control needs to be exercised over BCG aggregation, freeze-drying and powder compaction conditions to minimise physical damage of the bacterial cell wall and maximise the viability of oral BCG vaccines prepared by dry powder compaction.

scholarly journals A Systematic Approach to the Development of Cilostazol Nanosuspension by Liquid Antisolvent Precipitation (LASP) and Its Combination with Ultrasound

2021 ◽  
Vol 22 (22) ◽  
pp. 12406
Author(s):  
Emilia Jakubowska ◽  
Bartłomiej Milanowski ◽  
Janina Lulek
Keyword(s):  
Particle Size ◽  
Dissolution Rate ◽  
Particle Morphology ◽  
Feed Concentration ◽  
Bottom Up ◽  
Antisolvent Precipitation ◽  
Process Characterization ◽  
Apparent Solubility ◽  
Poorly Soluble ◽  
Successful Approach

Nanosizing is an approach to improve the dissolution rate of poorly soluble drugs. The first aim of this work was to develop nanosuspension of cilostazol with liquid antisolvent precipitation (LASP) and its combination with ultrasound. Second, to systematically study the effect of bottom-up processing factors on precipitated particles’ size and identify the optimal settings for the best reduction. After solvent and stabilizer screening, in-depth process characterization and optimization was performed using Design of Experiments. The work discusses the influence of critical factors found with statistical analysis: feed concentration, stabilizer amount, stirring speed and ultrasound energy governed by time and amplitude. LASP alone only generated particle size of a few microns, but combination with ultrasound was successful in nanosizing (d10 = 0.06, d50 = 0.33, d90 = 1.45 µm). Micro- and nanosuspension’s stability, particle morphology and solid state were studied. Nanosuspension displayed higher apparent solubility than equilibrium and superior dissolution rate over coarse cilostazol and microsuspension. A bottom-up method of precipitation-sonication was demonstrated to be a successful approach to improve the dissolution characteristics of poorly soluble, BCS class II drug cilostazol by reducing its particle size below micron scale, while retaining nanosuspension stability and unchanged crystalline form.

Sign in / Sign up

Export Citation Format

Share Document