VIVAPUR® MCG

VIVAPUR^® MCG - A Powerful Tool For Liquid Dosage Forms

INTRODUCTION

Liquid dosage forms are a common and popular approach to overcoming the many obstacles of administering medicines to children, the elderly, and animals. However, instabilities such as sedimentation, flocculation, or caking – especially in suspensions – are major challenges in the development of new formulations. VIVAPUR^® MCG addresses those challenges and allows a custom balance of rheological properties to guarantee high content uniformity and excellent long-term stability in suspensions, without the need for an excessive increase in viscosity.

VIVAPUR^® MCG is a synergistic, co-processed composite consisting of microcrystalline cellulose (MCC) and sodium carboxymethylcellulose (Na-CMC). It is a unique suspending and emulsifying agent, which facilitates a wide range of liquid dosage forms. Due to its extraordinary stabilizing mechanism, VIVAPUR^® MCG can be used with a broad variety of active pharmaceutical ingredients (APIs), offering the opportunity for new applications and line extensions for existing products.

WHAT IS VIVAPUR^® MCG?

VIVAPUR^® MCG is a free-flowing powder consisting of microcrystalline cellulose (MCC) and sodium carboxymethyl cellulose (Na-CMC). It is more than just a physical blend; the Na-CMC is interwoven with the microcrystalline cellulose, resulting in unique synergistic properties. The Na-CMC acts as a protective colloid to prevent the re-aggregation of the microcrystalline cellulose and ensures easy dispersibility.

BENEFITS

Convenience

Easy handling of the dry powder:
Excellent flow
Long shelf-life stability
Hassle-free handling of the activated gel:
Easy cleaning of the equipment
Ideal pumpability
Full functionality in hot and cold water
Robust versatile stabilizer:
Stable over a wide pH range
Sterilizable and freeze / thaw stable
Compatible with a wide range of ingredients
Combinable and synergistic with other stabilizers

High Acceptance

Negligible caloric value
Excellent sensory properties:
Odorless & tasteless
Smooth texture
Easy to swallow
Not sticky
Non-laxative
Accurate Dosage:
Ideal sprayability
Easy pumpability
Drop-by-drop dosing

APPLICATIONS

VIVAPUR^® MCG can be used with a variety of active pharmaceutical ingredients (APIs), offering the opportunity for new applications and line extensions for existing products. VIVAPUR^® MCG is used as a suspending agent, emulsifier, opacifier, and thickener for:

Oral suspensions
Veterinary drenches
Sprays (nasal, oral, or topical sprays)
Reconstitutable powders
Creams, gels, and lotions

REGULATORY BENEFITS

Halal /Kosher
Conforms with Ph.Eur./USP
GMO/BSE/TSE free
cGMP production standards
Non-animal origin
Conforms to the residual solvents requirement of USP <467
Allowable for animal health products, pediatric suspensions, and nutraceuticals

VIVAPUR^® MCG - More than a Thickener

MECHANISM OF STABILIZATION

Reliable stabilization of particles in a suspension cannot be guaranteed solely by high viscosity because this only slows down settlement. VIVAPUR^® MCG is more than just a thickener. After activation in water, VIVAPUR^® MCG forms a three-dimensional elastic gel-network of insoluble cellulose fibrils, building a yield point. The yield point is the minimum shear stress required to initiate flow. The suspension is stable if the force of gravity operating on the particle mass does not exceed the liquid‘s yield point. All particles can be kept homogeneously within the sustaining network and are prevented from settling.

VIVAPUR^® MCG - The Gel that Exhibits Fluid Properties

Upon agitation, MCG dispersions show a time- and shear-dependent decrease in viscosity and become liquid. A complete, also time-dependent, regeneration of viscosity takes place during a subsequent rest period. This so-called “thixotropic behavior” allows:

Outstanding sprayability of sprays
User-friendly dosing via drenches and dispensers
Accurate dosage of oral suspensions
Hassle-free handling of the activated gel
Ideal pumpability
Smooth and pleasant swallowing
Excellent content uniformity

Upon agitation, such as shaking of a medicine bottle, the cellulose fibrils arrange themselves in the direction of the movement. Thereby, the network loosens up and viscosity decreases. Thus, the dosage form becomes liquid and can be easily poured out of the bottle and measured. Soon after the movement ceases, the cellulose fibrils entangle again and form a three-dimensional network. The dispersions regain their full stabilizing ability, resulting in long-term stability and content uniformity.

VIVAPUR^® MCG Grades – Different Solutions for a Variety of Applications

GRADES

The available grades, VIVAPUR^® MCG 581, 591, 611 and 811 P, are distinguished by a varying, viscosity, elasticity, and Na-CMC content (Tab. 1). For nutraceutical applications, an additional grade ( VIVAPUR^® MCG 900X F) is available. Recommended use levels are 0.5 - 3,0% and depend on grade and desired function.

The density of the MCG network depends on the concentration of the applied VIVAPUR^® MCG (Fig. 1). The higher the concentration, the tighter the network and the better the retention of any particulate matter, such as the API. Thus, the required performance and viscosity can easily be adjusted by the concentration used. The viscosity increases mainly within the first hour and remains constant after 24hours.

VIVAPUR^® MCG 811 P - YOUR FIRST CHOICE

VIVAPUR^® MCG 811 P is JRS PHARMA's newest MCC / NaCMC composite for ready-to-use suspensions, nasal sprays, gels, and emulsions.

BENEFITS INCLUDE:

Superior particle stabilizing performance
Lower susceptibility to acids and salts compared to 591 and 581 types
Lower levels needed due to highest viscosity
(Fig. 1), elasticity (Fig. 2), and yield point

Fig. 1 Effect of the Concentration of Different VIVAPUR^® MCG Types on the Resulting Viscosity Directly after Activation (30 s) and after 24 h Settling Time.

Fig. 2 The Gel-Point Occurs after a Few Seconds to Minutes of Settling Time and Ensures a Rapid Stabilization of Particles. The Gel Point (Sol-Gel Transition) is Defined as the Intersection of the Modulus of Viscosity (G'', Dotted Line) and Elasticity (G', solid line). Different Types of VIVAPUR^® MCG were Measured by Oscillation Rheometry at a 3 % w / v Level

Characteristics of Different Grades of VIVAPUR^® MCG
VIVAPUR^® MCG	581 P	591 P	611 P	811 P
Viscosity after 30 s	72 – 168 m Pas (1.2 %)	39 – 91 mPa s (1.2 %)	50 – 118 mPa s (2.6 %)	2400 – 5600 mPa s (2.6 %)
Elasticity G'360S (3 %)	22 Pa	24 Pa	2 Pa	60 Pa
Gel-Point (3 %)	5 s	5 s	184 s	2 s
CMC-Na Content	8.3 – 13.8 %	8.3 – 13.8 %	11.3 – 18.8 %	11.3 – 18.8 %
Particle Size	> 250 µm max. 0.1 % > 75 µm max. 35 %	> 250 µm max. 0.1 % > 45 µm max. 45 %	> 250 µm max. 0.1 % > 45 µm max. 50 %	> 250 µm max. 3 %
Applications	Oral Suspensions, Sprays, Drenches, Gels, Emulsions	Oral Suspensions, Sprays, Drenches, Gels, Emulsions	Reconstitutable Powders	Oral Suspensions, Sprays, Drenches, Gels, Emulsions

a G'=Modulus of Elasticity is an Indicator for the Stabilizing Performance of the Gel Network. Measured by Oscillation Rheometry. The Higher G', the Better the Stability.

VIVAPUR^® MCG - Practical Advice & Exemplary Formulations

BASIC PREPARATION OF READY-TO-USE SUSPENSIONS AND SPRAY APPLICATIONS

Disperse VIVAPUR^® MCG in de-ionized water with low shear force (max. 5 % w/w). Do not add any other ingredients at this stage.
Apply high shear (Pic. 1) (colloidal mill at max. rpm. 3 – 10 min; homogenizer min. 150 bar). After activation, the suspension must have a rest period of at least 15 minutes
Dissolve the remaining soluble ingredients in the remaining water/liquid phase. Mix the liquids and remaining ingredients under medium stirring.
Adjust to final volume and pH and/or sterilize as required. Avoid air intake, particularly in steps 2 and 3.

Pic. 1 Preparation of VIVAPUR^® MCG dispersion

NASAL SPRAYS

Dispersible cellulose is a multifunctional and commonly used stabilizer for nasal sprays containing APIs such as Fluticasone, Budesonide, Beclomethasone, Triamcinolone Acetonide or Oxymetazoline Hydrochloride.

The VIVAPUR^® MCG gel network keeps the drug particles suspended in the main reservoir of the delivery device. During pumping, the gel becomes fluid in the delivery device and enables eased spraying and efficient, standardized atomization. After administration, the fluid regains its viscosity. Dripping from the nose or outflow into the throat area are prevented and retention time of the API in the nasal cavity is prolonged.

RECONSTITUTABLE POWDERS FOR PREPARATION OF AN ORAL SUSPENSION

Many antibiotics are prone to degradation in aqueous environments and thus expire quickly in liquid form. In order to obtain a long shelf-life, it is advisable to package the medicine without water and reconstitute just before the first intake. VIVAPUR^® MCG is the recommended grade for reconstitution and provides the following advantages:

Easy to activate by manual shaking
Reliable functionality irrespective of the grades of water hardness used
Maintains content uniformity of the API
Reliable prevention of particle sedimentation
Accurate dosage
Long-term stability
Enhanced pH, salt, and temperature tolerance
Highly thixotropic

VIVAPUR^® MCG - The Highly Compatible, Robust, and Versatile Stabilizer

COMPATIBILITY

VIVAPUR^® MCG is compatible with a wide range of ingredients commonly used for suspensions, such as sugars, sugar alcohols, artificial sweeteners, wetting agents, alcohols, nonionic surfactants or preservatives (Fig. 3).
VIVAPUR^® MCG:

Withstands sterilization and long-term heating (Fig. 4)
Shows excellent freeze thaw stability
Can be dispersed in hot or cold water
Stable in a wide pH range (3.8 – 10)

Up to ~2 % w / v (VIVAPUR^® MCG 591 P and 811 P) and 5 % w / v (VIVAPUR^® MCG 611 P) sodium chloride salt is tolerated if it is added after the MCG has been activated in distilled water. If higher amounts of soluble buffer salts, di- or trivalent cations, are part of the suspension, additional protective colloids (8 - 30 % related to the total amount of MCG), such as xanthan, methylcellulose, or HPMC are recommended to prevent a flocculation of the gel network.

The nutraceutical grade VIVAPUR^® MCG 900X F is coprocessed with Xanthan. It provides maximum pH and salt tolerance.

SENSORY ADVANTAGES

Activated MCG builds an opaque-white dispersion which masks insoluble particles, giving the suspension a homogeneous appearance.

The dispersed VIVAPUR^® MCG is characterized by an odorless and tasteless, smooth but not slimy mouthfeel, and handles flavors well, which is essential for pediatric products.

Fig. 3 VIVAPUR^® MCG is Compatible with a Wide Range of Common Ingredients

Fig. 4 Effect of Temperature on the Viscosity of a MCG Dispersion (2 % w/v). Viscosity was Measured by a Brookfield Viscometer after Heat Treatment and Subsequent Re-cooling to 25 °C

PACKAGING, SAMPLES AND STORAGE

Storage

Protect from excessive heat and moisture

Packaging

25 kg paper bag with polyethylene liner

1 Europallet contains 24 bags 25 kg = 600 kg

Custom tariff '3912 90 90

Sample Sizes

400 g Aluminium pouch

2 kg Aluminium pouch

Microcrystalline Cellulose and Carboxymethylcellulose Sodium

VIVAPUR® MCG - A Powerful Tool For Liquid Dosage Forms