List of Narcotics Precursor : The Legal and Illegal Used

Precursor is a chemical used in the manufacture of drugs that are in control. In general, the precursors used legally / officially in industrial processes and most traded in international trade.

The chemical is not in the special supervision, but the export and import and supply of precursors to individuals and companies whose use is not for use in industry is a clue that there is a possibility of these activities are illegal activities.

Precursor term used for materials that are not narcotic, but used in a variety of ways to process or make the narcotics or psychotropic substances.

Depending on their chemical properties, chemical precursors can be joined with other substances to be used as drug (or in the form of intermediaries), or can work as an acidic substance.

Here is a list of some of the precursors to manufacture legal drugs and materials commonly used in various industries.

Manufacturing of Ethanol in Industrial Scale by Hydration of Ethane Method and Fermentation Method

Manufacturing of Ethanol by Hydration of Ethane Method

Ethanol is manufactured by reacting ethene with steam. The catalyst used is silicon dioxide which is coated with a solid phosphoric acid.The reaction is reversible, and the formation of the ethanol is exothermic.

Only 5% of the ethene is converted into ethanol at each pass through the reactor. By removing the ethanol from the equilibrium mixture and recycling the ethene, it is possible to achieve an overall 95% conversion.

A flow scheme for the reaction looks like this:

Note: This is a bit of a simplification! When the gases from the reactor are cooled, then excess steam will condense as well as the ethanol. The ethanol will have to be separated from the water by fractional distillation.

Manufacturing Process of Nata de Coco

Nata is a product of fermentation of the bacterium Acetobacter xylinum in the form of sheets of cellulose from the conversion of sugars contained in the substrate (typically coconut water but can also be of other materials) into pelikel cellulose. The main content of nata de coco is water and fiber, which is good for diet and is often used in the manufacture of dessert or as an additional substance in the cocktail, ice cream and so on. Things that need to be considered in making nata include bacteria, sugars and nitrogen, but it should also be noted as well as temperature and pH, do not swayed to the formation of pelikel going well.

 Nata de Coco

Acetobacter xylinum bacteria are Gram-negative bacteria that can synthesize cellulose from fructose. Cellulose has a pore across on the mini glucan crystals which then coalitioned in microfibrils. Microfibril clusters that exist in the structure of the compounds formed as the ribbons that can directly observed using microscope.

Manufacturing Step of Nata De Coco

1. Preparation of starter media / Nata De Coco Seed
Microbial starter culture is the most important ingredient in the formation of nata. As a starter, used pure cultures of Acetobacter xylinum. These bacteria can be produced from pineapple pulp that has been incubated (brooded) for 2-3 weeks. Starter used in the manufacture of nata of 170 ml.


COLOUR SUBSTANCES CONTAINED IN THE NATURAL FOOD DYES

Some examples of natural dyes used for coloring foods are:

ANTHOCYANINS, the cause of red, orange, purple and blue found in many fruits and flowers like roses, water henna, hibiscus, flower beads / kana, chrysanthemum, pelargonium, china aster, and apples, Chery, grapes, strawberries , also found in the mangosteen fruit and sweet potato tubers. Blue pea flowers, produces a purplish blue color. Star fruit flowers produce red color. The use of natural dyes, such as anthocyanin pigments are still limited to some food products, such as beverage products (juice and milk).

Anthocyanin is a derivative of a single aromatic structure, namely cyanidin. Anthocyanin is flavonoids that structurally include in flavone group. Anthocyanins are natural antioxidants that can prevent cancer, heart disease, high blood pressure, cataracts, and even smoothing the skin.
Anthosianin pigment color red, blue, violet and are usually found on flowers, fruits and vegetables. The pigments color are influenced by the concentration of pigment, and pH. At dilute concentrations, anthocyanin is blue, in contrast to the dense concentration, the color is red and at usual concentration is purple. At low pH anthocyanin pigment is red and at high pH changed to violet and then to blue.

BIKSIN, giving yellow like butter. Biksin obtained from the seeds of Bixa Orellana tree found in tropical areas and is often used to color butter, margarine, corn oil and salad dressings.

NATURAL DYES USED IN FOOD

You are love to make your own snacks must be more selective in choosing a variety of materials used, including the selection of food coloring. Selection of food coloring is not without reason, this additional material will support the appearance of food or drink that you serve.

Here are a source of natural dyes you can use:

Red

To make your food become red, you can use red yeast rice (Angkak or red kojic rice) or rosella flower corolla. Red yeast rice is fermented from red rice.

How to use red yeast rice : red yeast rice brewed with hot water, discard the first soaking water, do up to three times. After the third infusion, mash the red yeasr rice and ready for use as natural food colorants. For rosella flowers, brewed rosella flowercorolla, then mash and ready mixed as a red dye.
 Angkak or Red yeast rice

Factors Influencing Encapsulation Efficiency

The encapsulation efficiency of the microparticle or microcapsule or microsphere will be affected by different parameters.








Factors influencing encapsulation efficiency

High solubility of polymer in organic solvent Slow solidification of microparticle Low encapsulation efficiency
Low solubility of organic solvent in water
Low concentration of polymer
High DP/CP ratio
Slow solvent removal


Low solubility of polymer in organic solvent Fast solidification of microparticle High encapsulation efficiency
High solubility of organic solvent in water
High concentration of polymer
Low DP/CP ratio
Fast solvent removal

TECHNIQUES TO MANUFACTURE MICROCAPSULES BY PHYSICO-MECHANICAL PROCESS

Pan coating

The pan coating process, widely used in the pharmaceutical industry, is among the oldest industrial procedures for forming small, coated particles or tablets. The coating solution is applied as atomized spray to the solid core material in the coating pan. To remove the coating solvent warm air is passed over the coated material. By using this technique larger sized particles will be coated effectively.

Air-Suspension Coating

Air-suspension coating of particles by solutions or melts gives better control and flexibility. The particles are coated while suspended in an upward-moving air stream. They are supported by a perforated plate having different patterns of holes inside and outside a cylindrical insert. Just sufficient air is permitted to rise through the outer annular space to fluidize the settling particles. Most of the rising air (usually heated) flows inside the cylinder, causing the particles to rise rapidly. At the top, as the air stream diverges and slows, they settle back onto the outer bed and move downward to repeat the cycle. The particles pass through the inner cylinder many times in a few minutes.

Centrifugal Extrusion

Centrifugal extrusion processes generally produce capsules of a larger size, from 250 microns up to a few millimeters in diameter. Liquids are encapsulated using arotating extrusion head containing concentric nozzles. In this process, a jet of core liquid is surrounded by a sheath of wall solution or melt. As the jet moves through the air it breaks, owing to Rayleigh instability, into droplets of core, each coated with the wall solution. While the droplets are in flight, a molten wall may be hardened or a solvent may be evaporated from the wall solution. Since most of the droplets are within ± 10% of the mean diameter, they land in a narrow ring around the spray nozzle. Hence, if needed, the capsules can be hardened after formation by catching them in a ring-shaped hardening bath. This process is excellent for forming particles 400-2,000 µm (16-79 mils) in diameter. Since the drops are formed by the breakup of a liquid jet, the process is only suitable for liquid or slurry. A high production rate can be achieved, i.e., up to 22.5 kg (50 lb) of microcapsules can be produced per nozzle per hour per head.

TECHNIQUES TO MANUFACTURE MICROCAPSULES BY PHYSICO-CHEMICAL METHODS

Coacervation and phase separation

Is a partial desolvation of a homogeneous polymer solution into a polymer-rich phase (coacervate) and the poor polymer phase (coacervation medium). Currently, two methods for coacervation are available, namely simple and complex processes. The mechanism of microcapsule formation for both processes is identical, except for the way in which the phase separation is carried out. In simple coacervation a desolvation agent is added for phase separation, whereas complex coacervation involves complexation between two oppositely charged polymers.

The three basic steps in complex coacervation are:
(i) formation of three immiscible phases
(ii) deposition of the coating
(iii) rigidization of the coating

First step : formation of three immiscible phases; liquid manufacturing vehicle, core material, coating material. The core material is dispersed in a solution of the coating polymer. The coating material phase, an immiscible polymer in liquid state is formed by :
  1. changing temperature of polymer solution, e.g. ethyl cellulose in cyclohexane
  2. addition of salt, e.g. addition of sodium sulphate solution to gelatine solution in vitamin encapsulation
  3. addition of nonsolvent, e.g. addition of isopropyl ether to methyl ethyl ketone solution of cellulose acetate butyrate
  4. addition of incompatible polymer to the polymer solution, e.g. addition of polybutadiene to the solution of ethylcellulose in toluene
  5. inducing polymer – polymer interaction, e.g. interaction of gum Arabic and gelatine at their iso-electric point. 

TECHNIQUES TO MANUFACTURE MICROCAPSULES BY CHEMICAL METHODS

Interfacial Polymerization (IFP)

In Interfacial polymerization, the two reactants in a polycondensation meet at an interface and react rapidly. The basis of this method is the classical Schotten-Baumann reaction between an acid chloride and a compound containing an active hydrogen atom, such as an amine or alcohol, polyesters, polyurea, polyurethane. Under the right conditions, thin flexible walls form rapidly at the interface. A solution of the pesticide and a diacid chloride are emulsified in water and an aqueous solution containing an amine and a polyfunctional isocyanate is added. Base is present to neutralize the acid formed during the reaction. Condensed polymer walls form instantaneously at the interface of the emulsion droplets.

In situ polymerization

Like IFP the capsule shell formation occurs because of polymerization monomers added to the encapsulation reactor. In this process no reactive agents are added to the core material, polymerization occurs exclusively in the continuous phase and on the continuous phase side of the interface formed by the dispersed core material and continuous phase. Initially a low molecular weight prepolymer will be formed, as time goes on the prepolymer grows in size, it deposits on the surface of the dispersed core material there by generating solid capsule shell. E.g. encapsulation of various water immiscible liquids with shells formed by the reaction at acidic pHof urea with formaldehyde in aqueous media. . In one process, e.g. Cellulose fibers are encapsulated in polyethylene while immersed in dry toluene. Usual deposition rates are about 0.5ìm/min. Coating thickness ranges 0.2-75 µm(0.0079-2.95 mils). The coating is uniform, even over sharp projections.

TECHNIQUES TO MANUFACTURE MICROCAPSULES - MICROENCAPSULATION

Microencapsulation may be defined as the process of surrounding or enveloping one substance within another substance on a very small scale, yielding capsules ranging from less than one micron to several hundred microns in size. The product obtained by this process is called as micro particles, microcapsules, microspheres which differentiate in morphology and internal structure.

When the particle size is below 1µm are known as nanoparticles, nanocapsules, nanospheres respectively and particles having diameter between 3 - 800µm are known as micro particles or microcapsules or microspheres. Particles larger than 1000µm are known as macroparticles.

Microcapsules may be spherically shaped, with a continuous wall surrounding the core, while others are asymmetrically and variably shaped, with a quantity of smaller droplets of core material embedded throughout the microcapsule. All three states of matter (solids, liquids, and gases) may be microencapsulated. This allows liquid and gas phase materials to be handled more easily as solids, and can afford some measure of protection to those handling hazardous materials.

Micro particles or microcapsules consist of two components namely core material and coat or shell material. The substance that is encapsulated may be called the core material, the active ingredient or agent, fill, payload, nucleus, or internal phase. The material encapsulating the core is referred to as the coating, membrane, shell, or wall material. Microcapsules may have one wall or multiple shells arranged in strata of varying thicknesses around the core.

Overcome Diarrhea In Children with Probiotic

Diarrhea is the leading cause of death in children in the world, accounting for 50-10 million deaths / year. How diarrhea occurs? Diarrhea occurs because the amount of more bad bacteria than good bacteria. In children often found diarrhea caused by food sources that are less hygienic and dirt contamination.

Microorganisms that benefit the body or bacteria known as probiotics are not only useful for maintaining digestive health. Probiotics can also be used as a drug used to treat diarrhea. Probiotics are beneficial non-pathogenic bacteria that live in colonies in the small intestine and can cause changes in gut microflora and affect the metabolic activity with a favorable outcome for the hosts.

Treatment of diarrhea with the use of good bacteria, is relatively rare, Though using probiotics to treat diarrhea safer and better than using chemical drugs or antibiotic. Besides treating diarrhea, efficacious probiotic to streamline and improve other digestive disorders like constipation.

Bacteria Used as Prebiotics

Lactobacillus and Bifidobacterium in general is non-pathogenic bacteria, because they are naturally present in the gut. Not all acid-resistant bacteria have probiotic effects. Multiple strains of probiotics is more effective than single strains.

Mechanism of Tablet Disintegrants

There are seven major mechanisms for tablets disintegration as follows

1. Swelling:
Perhaps the most widely accepted general mechanism of action for tablet disintegration is swelling. Swelling is believed to be a mechanism in which certain disintegrating agents (such as starch) impart the disintegrating effect. By swelling in contact with water, the adhesiveness of other ingredients in a tablet is overcome causing the tablet to fall apart. Tablets with high porosity show poor disintegration due to lack of adequate swelling force. On the other hand, sufficient swelling force is exerted in the tablet with low porosity. It is worthwhile to note that if the packing fraction is very high, fluid is unable to penetrate in the tablet and disintegration is again slows down.



Particles swell and break up the matrix form within









Techniques and Technology for Manufacturing Fast Dissolving Tablets (Part II)

Sublimation

To generate a porous matrix, volatile ingredients are incorporated in the formulation that is later subjected to a process of sublimation. Highly volatile ingredients like ammonium bicarbonate, ammonium carbonate, benzoic acid, camphor, naphthalene, urea, urethane and phthalic anhydride may be compressed along with other excipients into a tablet. This volatile material is then removed by sublimation leaving behind a highly porous matrix. Tablets manufactured by this technique have reported to usually disintegrate in 10-20 sec. Even solvents like cyclohexane; benzene can be used as pore forming agents.

The key to rapid disintegration for mouth dissolving tablets is the presence of a porous structure in the tablet matrix. Conventional compressed tablets that contain highly water-soluble ingredients often fall to dissolve rapidly because of low porosity of the matrix. Hence. To generate porous matrix, volatile ingredients are used that are later subjected to a process of sublimation.



Schematic Diagram of Sublimation Technique for Preparation of MDT


Techniques and Technology for Manufacturing Fast Dissolving Tablets (Part I)

Many techniques have been reported for the formulation of Fast dissolving tablets or Orodispersible tablets.

1. Freeze drying / lyophilization
2. Tablet Moulding
3. Spray drying
4. Sublimation
5. Direct compression
6. Mass extrusion
7. Melt granulation
8. Phase transition process
9. Cotton Candy Process


Freeze-Drying or Lyophilization 

Freeze drying is the process in which water is sublimed from the product after it is frozen. Freeze-dried forms offer more rapid dissolution than other available solid products. The lyophilization process imparts glossy amorphous structure to the bulking agent and sometimes to the drug, thereby enhancing the dissolution characteristics of the formulation.

Formulation and Excipients Used in Fast Dissolving Tablet (FDT)

In formulating Fast Dissolving Tablet/Oral Disintegrated Tablet, additional excipients are likely to include a suitable flow aid and lubricant for tablet manufacture. Because the tablet is intended to dissolve in the mouth, ODTs often include flavors and sweeteners to mask the taste of bitter actives. Finally, color may be added to the formulation to add elegance and to aid in identification of the final dosage form.

In the formulation of FDT the most important additives are as fallows

1. Superdisintegrants

Fast Dissolving Tablet require faster disintegration, that’s why superdisintegrants is needed in formulating FDT/ODT. Superdisintegrant used is the one that effective at low concentration and have greater disintegrating efficiency and they are more effective intragranularly. The problem is, it is hygroscopic therefore not used with moisture sensitive drugs.

Superdisintegrants Used in Tablet

Disintegrating agents are substances routinely included in the tablet formulations to aid in the break up of the compacted mass when it is put into a fluid environment. They promote moisture penetration and dispersion of the tablet matrix.

These newer substances are more effective at lower concentrations with greater disintegrating efficiency and mechanical strength. On contact with water the superdisintegrants swell, hydrate, change volume or form and produce a disruptive change in the tablet. Effective superdisintegrants provide improved compressibility, compatibility and have no negative impact on the mechanical strength of formulations containing high-dose drugs.

List of Superdisintegrant

EXAMPLESUPER-DISINTEGRANTSMECHANISM OF ACTIONSPECIAL COMMENT
Crosslinked cellulose
Crosscarmellose®
Ac-Di-Sol®
Primellose® 
Vivasol®

Swells 4-8 folds in <10 seconds.

Swelling and wicking both.

Swelling is in two dimensions.
-Direct compression or granulation
-Starch free
Crosslinked PVPCrosspovidone
Kollidon
Polyplasdone
Swells 7-12 folds in <30  seconds

Swells very little and returns to original size after compression but act by capillary action
Swells in three dimensions and high level serve as sustain release matrix

Water insoluble and spongy in nature so get porous tablet
Crosslinked starch
Sodium Starch Glycolate
Swells 7-12 folds in <30  secondsSwells in three dimensions and high level serve as sustain release matrix
Crosslinked alginic acidAlginic acid NF
Satialgine
Rapid swelling in aqueous medium or wicking actionPromote disintegration in both dry  or wet granulation
Natural super DisintegrantsSoy polysaccharides
Emcosoy
Rapid DissolvingDoes not contain any starch or sugar. Used in nutritional products.

Calcium SilicateWicking actionHighlyporous, Optimum concentration is between 20-40%

Fast Dissolving Tablet – Oral Dispersible Tablet : Complete Review

Oral drug administration has been one of the most suitable and widely accepted by the patients for the delivery of most therapeutically active drugs. Various dosage forms like tablets, capsules and liquid preparations have been administered by oral route. But, due to some unsuitable physiological conditions of the gastro-intestinal tract such as :
  • relatively poor absorption
  • presence of various digestive enzymes of the gastro-intestinal lumen and epithelium
  • poor absorption efflux (i.e. by P-glycoprotein, etc.)
  • first pass metabolism by hepatic enzymes
the administration of some drugs is affected. Fast- or mouth dissolving tablets have been formulated for pediatric, geriatric, and bedridden patients and for active patients who are busy and traveling and may not have access to water. Such formulations provide an opportunity for product line extension in the Many elderly persons will have difficulties in taking conventional oral dosage forms (viz., solutions, suspensions, tablets, and capsules) because of hand tremors and dysphagia. Swallowing problems also are common in young individuals because of their underdeveloped muscular and nervous systems. Other groups that may experience problems using conventional oral dosage forms include the mentally ill, the developmentally disabled, and patients who are uncooperative, on reduced liquid-intake plans, or are nauseated. In some cases such as motion sickness, sudden episodes of allergic attack or coughing, and an unavailability of water, swallowing conventional tablets may be difficult.

Search