COMPARATIVE EVALUATION OF THE RELEASE PROPERTIES OF VERAPAMIL HCL AND CARBAMAZEPINE FROM MICROCRYSTALLINE CELLULOSE II PELLETS

Objective: To study microcrystalline cellulose II (MCCII) as new pelletization aid for a high and low solubility drugs such as verapamil. HCl and carbamazepine, respectively.Methods: Approximately, 30 g of MCCII and drug mixtures were hydrated passed through a # 20 mesh sieved and spheronizated at a frequency of 6 Hz and residence time of 480 s. A microscopy analysis was used to evaluate the shape and size descriptors. Pellets properties such as compressibility, friability, density, flowability and product yield were also evaluated. Drug release properties were tested according to the USP specifications and compared to those of MCCI.Results: The wetting level of the excipients depended on drug loading and drug solubility. Thus, a high drug loading (>50%) rendered pellets having a low yield, flowability and caused a detriment on size descriptors. Likewise, the regular morphology and strength of MCCII-based pellets was highly affected by increasing drug loads. Verapamil. HCl pellets were less friable and compressible and showed better flowability than carbamazepine pellets. Regardless of drug loading and drug solubility, MCCII-based pellets released more than 80% of verapamil. HCl within 10 min, whereas released more than 75% of carbamazepine within 15 min. Conversely, MCCI pellets had a satisfactory verapamil. HCl release, but ~30% carbamazepine release within 1h.Conclusion: MCCII proved to be a better excipient than MCCI to yield beads having optimal pellet characteristics and rendered an immediate release profile for verapamil. HCl and carbamazepine.

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ASSESSMENT OF THE PRODUCTION VARIABLES ON THE PELLETIZATION PROPERTIES OF MICROCRYSTALLINE CELLULOSE II (MCCII)

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2017v9i10.20580 ◽

2017 ◽

Vol 9 (10) ◽

pp. 73

Author(s):

John Rojas ◽

David Correa

Keyword(s):

Microcrystalline Cellulose ◽

Total Porosity ◽

Operating Conditions ◽

Cellulose Ii ◽

Shape Descriptors ◽

Pellet Size ◽

Surface Design ◽

Operational Conditions ◽

High Moisture Level ◽

Pelletization Aid

Objective: To study microcrystalline cellulose II (MCCII) as new pelletization aid using the extrusion/spheronization technology.Methods: The effect of the spheronization rate and spheronization time was assessed by a response surface design. The shape descriptors and physical properties of pellets were taken as response variables. Approximately, 30 g of MCCII were hydrated, passed through a # 20 mesh sieve and spheronizated at frequencies of 6, 9 and 12 Hz and residence times of 15, 240 and 480 s in 9 experimental runs. In a separate experimental set, moisture levels of 25, 50, 75, 100 and 125% were employed at the optimal operating conditions of 6 Hz and 480 s. A microscopy analysis was used to evaluate the shape descriptors. Pellets properties such as compressibility, friability, porosity, strength, flow rate and mass were also evaluated.Results: Pellets having a small size and a high value of shape descriptors related to morphology were obtained employing a spheronization rate and spheronization time of 6Hz and 480s and 100% wetting level. The spheronization time increased pellet densification but decreased the total porosity. Pellet mass was also favoured by using high spheronization rates. A high moisture level (>100%) rendered pellets having a large size, mass, low porosity and good yield. Conversely, pellet size decreased as sample load increased, whereas porosity and compressibility increased as sample load augmented.Conclusion: MCCII offers the potential for use as an alternative pelletization agent rendering pellets having a good flowability, high mechanical strength and low friability at the optimal operational conditions.

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Co-Loading of Temozolomide and Curcumin into a Calix[4]arene-Based Nanocontainer for Potential Combined Chemotherapy: Binding Features, Enhanced Drug Solubility and Stability in Aqueous Medium

Nanomaterials ◽

10.3390/nano11112930 ◽

2021 ◽

Vol 11 (11) ◽

pp. 2930

Author(s):

Rossella Migliore ◽

Nicola D’Antona ◽

Carmelo Sgarlata ◽

Grazia M. L. Consoli

Keyword(s):

Isothermal Titration Calorimetry ◽

Anticancer Drugs ◽

Drug Loading ◽

Building Blocks ◽

Critical Micellar Concentration ◽

Titration Calorimetry ◽

Drug Solubility ◽

New Paradigm ◽

Drug Combination Therapy ◽

Low Solubility

The co-delivery of anticancer drugs into tumor cells by a nanocarrier may provide a new paradigm in chemotherapy. Temozolomide and curcumin are anticancer drugs with a synergistic effect in the treatment of multiform glioblastoma. In this study, the entrapment and co-entrapment of temozolomide and curcumin in a p-sulfonato-calix[4]arene nanoparticle was investigated by NMR spectroscopy, UV-vis spectrophotometry, isothermal titration calorimetry, and dynamic light scattering. Critical micellar concentration, nanoparticle size, zeta potential, drug loading percentage, and thermodynamic parameters were all consistent with a drug delivery system. Our data showed that temozolomide is hosted in the cavity of the calix[4]arene building blocks while curcumin is entrapped within the nanoparticle. Isothermal titration calorimetry evidenced that drug complexation and entrapment are entropy driven processes. The loading in the calixarene-based nanocontainer enhanced the solubility and half-life of both drugs, whose medicinal efficacy is affected by low solubility and rapid degradation. The calixarene-based nanocontainer appears to be a promising new candidate for nanocarrier-based drug combination therapy for glioblastoma.

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Use of crospovidone as pelletization aid as alternative to microcrystalline cellulose: effects on pellet properties

Drug Development and Industrial Pharmacy ◽

10.1080/03639040902902401 ◽

2009 ◽

pp. 090526005142032-8

Author(s):

P. Verheyen ◽

K.-J. Steffens ◽

P. Kleinebudde

Keyword(s):

Microcrystalline Cellulose ◽

Pelletization Aid

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Present trends in the encapsulation of anticancer drugs

Physical Sciences Reviews ◽

10.1515/psr-2020-0080 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Xavier Montané ◽

Karolina Matulewicz ◽

Karolina Balik ◽

Paulina Modrakowska ◽

Marcin Łuczak ◽

...

Keyword(s):

Carbon Nanotubes ◽

Drug Toxicity ◽

Recent Progress ◽

Polymeric Micelles ◽

Drug Loading ◽

The Body ◽

Inorganic Nanoparticles ◽

Hybrid Nanoparticles ◽

Traditional Medicines ◽

Low Solubility

Abstract Different nanomedicine devices that were developed during the recent years can be suitable candidates for their application in the treatment of various deadly diseases such as cancer. From all the explored devices, the nanoencapsulation of several anticancer medicines is a very promising approach to overcome some drawbacks of traditional medicines: administered dose of the drugs, drug toxicity, low solubility of drugs, uncontrolled drug delivery, resistance offered by the physiological barriers in the body to drugs, among others. In this chapter, the most important and recent progress in the encapsulation of anticancer medicines is examined: methods of preparation of distinct nanoparticles (inorganic nanoparticles, dendrimers, biopolymeric nanoparticles, polymeric micelles, liposomes, polymersomes, carbon nanotubes, quantum dots, and hybrid nanoparticles), drug loading and drug release mechanisms. Furthermore, the possible applications in cancer prevention, diagnosis, and cancer therapy of some of these nanoparticles have been highlighted.

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Stable, metastable and unstable cellulose solutions

Royal Society Open Science ◽

10.1098/rsos.170487 ◽

2017 ◽

Vol 4 (8) ◽

pp. 170487 ◽

Cited By ~ 10

Author(s):

Marta Gubitosi ◽

Pegah Nosrati ◽

Mona Koder Hamid ◽

Stefan Kuczera ◽

Manja A. Behrens ◽

...

Keyword(s):

Microcrystalline Cellulose ◽

Small Angle ◽

Supersaturated Solution ◽

Cellulose Ii ◽

Cellulose I ◽

Tetrabutylammonium Hydroxide ◽

X Ray ◽

Stable Regime ◽

X Ray Scattering ◽

A Minor

We have characterized the dissolution state of microcrystalline cellulose (MCC) in aqueous tetrabutylammonium hydroxide, TBAH(aq), at different concentrations of TBAH, by means of turbidity and small-angle X-ray scattering. The solubility of cellulose increases with increasing TBAH concentration, which is consistent with solubilization driven by neutralization. When comparing the two polymorphs, the solubility of cellulose I is higher than that of cellulose II. This has the consequence that the dissolution of MCC (cellulose I) may create a supersaturated solution with respect to cellulose II. As for the dissolution state of cellulose, we identify three different regimes. (i) In the stable regime, corresponding to concentrations below the solubility of cellulose II, cellulose is molecularly dissolved and the solutions are thermodynamically stable. (ii) In the metastable regime, corresponding to lower supersaturations with respect to cellulose II, a minor aggregation of cellulose occurs and the solutions are kinetically stable. (iii) In the unstable regime, corresponding to larger supersaturations, there is macroscopic precipitation of cellulose II from solution. Finally, we also discuss strong alkali solvents in general and compare TBAH(aq) with the classical NaOH(aq) solvent.

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Elution Behavior of Nizatidine Immediate Release Tablets According to Lactose and Microcrystalline Cellulose Content

Polymer Korea ◽

10.7317/pk.2020.44.4.566 ◽

2020 ◽

Vol 44 (4) ◽

pp. 566-571

Author(s):

Jun Jae Jung ◽

Jin Woo Kim ◽

Pil Yun Kim ◽

Won Kyung Kim ◽

Jeong Eun Song ◽

...

Keyword(s):

Microcrystalline Cellulose ◽

Immediate Release ◽

Cellulose Content ◽

Elution Behavior

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Systematic Development of Bicalutamide Immediate Release Pellets using Aeroperl and Non-MCC Extruder aid

Current Drug Therapy ◽

10.2174/1574885515999200424082315 ◽

2020 ◽

Vol 15 ◽

Author(s):

Hardik Rana ◽

Hussain Hasan ◽

Mukesh Gohel ◽

Vaishali Thakkar ◽

Tejal Gandhi

Keyword(s):

Drug Release ◽

Propylene Glycol ◽

Microcrystalline Cellulose ◽

Immediate Release ◽

Phase Solubility ◽

Disintegration Time ◽

Solubility Study ◽

Short Period ◽

Phase Solubility Study ◽

Pellet Formulation

Background: The Microcrystalline Cellulose is called as a gold standard for the manufacture of pellets. The poor disintegration leads to incomplete drug release restricts the use of MCC in the immediate-release formulation. Objective: The present work aims to explore non-MCC extruder aid for pellet formulation and solubility modulation potential of Aeroperl® 300 Pharma. Methods: Bicalutamide (BCL) was selected as a model BCS class-II drug. The solubility of BCL was assessed in different vehicles like polyethylene glycol, propylene glycol, and Tween by carrying out phase solubility study. The suitable vehicle was selected based on the higher solubility of BCL. The vehicle was further adsorbed on newer adsorbent Aeroperl® 300 Pharma to formulate liquisolid granules. The liquisolid granules were further incorporated into the pellet using mannitol and microcrystalline cellulose as an extruder aid. Box-Behnken design was adopted for optimization of formulation considering MCC: mannitol ratio, concentration of HPMC and spheronizer speed as independent factors whereas drug release at 30 min, disintegration time and aspect ratio were selected as dependent variables. The pellets were evaluated for different evaluation parameters. Results: Propylene glycol was selected for the formulation of liquisolid technique based on the results of the phase solubility study. Propylene glycol containing BCL was adsorbed on Aeroperl 300 Pharma. The optimized batch was selected exploring the Design-Expert software by considering limits of different responses. Pellet had excellent flowability. Friability was found to be within the range (<1%). Pellets were found to be spherical and had pores on the surfaces. Conclusion: Liquisolid granules containing newer solubilizer Aeroperl was found to be a promising approach for the improvement in the solubility of the drug. The use of mannitol with MCC has a profound effect on disintegration time, without altering flow property and other parameters. No patents were reported on the combination of Bicalutamide, mannitol and Aeroperl. The critical finding of the present work is to use mannitol as an extruder aid to fasten the disintegration leads to complete drug release within a short period of time. Aeroperl and Mannitol, MCC: mannitol ratio, concentration of HPMC and spheronizer speed was found to be significant and had the potential effect in pellet formulation.

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ENHANCEMENT OF THE IMMEDIATE RELEASE OF PARACETAMOL FROM ALGINATE BEADS

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2017v9i2.15672 ◽

2017 ◽

Vol 9 (2) ◽

pp. 47 ◽

Cited By ~ 2

Author(s):

Samah Hamed ◽

Farah Amalina Ayob ◽

Mulham Alfatama ◽

Abd Almonem Doolaanea

Keyword(s):

Drug Release ◽

Drug Loading ◽

Barium Chloride ◽

Tween 80 ◽

Immediate Release ◽

Alginate Beads ◽

Acidic Ph ◽

Needle Size ◽

Lower Drug ◽

Ph Sensitive Polymer

Objective: Alginate beads are not soluble in the acid leading to small portion released in the stomach. This may not be favourable for drugs administered for fast action like paracetamol. So, this study was aimed to increase the immediate release of paracetamol from alginate beads, i.e. the release in the acidic pH.Methods: The beads were prepared by dropwise paracetamol/alginate suspension in divalent cation solution. Two attempts were used to increase the dissolution of paracetamol in the acidic pH. First attempt was by only changing preparation variables: needle size, alginate viscosity and drug loading using 23 full factorial design. The second approach was by adding excipients like carbopol, tween and polyethylene glycol. The beads were characterized for their size, encapsulation efficiency and release profile.Results: First approach, changing preparation variables without excipient adding, helped to increase the drug release in the acid but to a maximum of 26% using a smaller needle, lower drug loading and higher alginate viscosity. However, optimising the formulation with suitable excipients increased the drug release in the acid to 77.3%. The optimised formulation included carbopol 940 (pH sensitive polymer) and tween 80 (facilitates water entry) in the beads, with using barium chloride instead of calcium chloride together with PEG 400 in the complexing solution.Conclusion: To achieve immediate release of paracetamol from alginate beads in the acidic pH, excipients need to be added. Rational selection of excipients is critical to achieve the desired drug release.

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