Microcapsules: types, preparation and evaluation

Microcapsules: introduction, types and evaluation

1. Microcapsules Presented by Mohammad Asim 20/MPH/DIPSAR/2019

2. Contents Introduction Reasons for Microencapsulation Types of microcapsules Formulation considerations Techniques for preparation of microcapsules Evaluation of microcapsules Applications of microcapsules in pharmacy 3 4 5 6 9 17 19

3. Introduction Microencapsulation is the process of enclosing a substance inside a miniature called capsule. Microcapsules are a small sphere with a uniform wall around it. The material inside the microcapsule is referred to as the core/ internal phase, whereas the wall is sometimes called a shell/coating. The microcapsule size range from 1 µ -7mm. All the 3 states i.e. solid, liquid and gases may be encapsulated which may affect the size and shape of capsules. If the solid or crystalline material is used as the core, the resultant capsule may be irregularly shaped. If the core material is liquid, simple spherical capsules containing a single droplet of encapsulate may be formed.

4. Reasons for Microencapsulation It is mainly used to increase the stability, and sustained/prolonged release of the product. Controlling the release rate of the drug from the microcapsules. This technique was widely used for masking taste and odor of many drugs and to improve patient compliance. For converting liquid drugs into a free flowing powder. To reduce the toxicity and GI irritation and many major side effects of the drugs. Alteration in site of absorption can be achieved by microencapsulation. In some cases, the core must be isolated from its surroundings, as in isolating vitamins from the deteriorating effects of oxygen. In retarding evaporation of a volatile core. To improve handling properties of a sticky material. To protect the GIT from irritant effects of drug, for example aspirin.

5. Mononuclear (core-shell) microcapsules contain the shell around the core. Polynuclear capsules have many cores enclosed within the shell. Matrix encapsulation in which the core material is distributed homogeneously into the shell material. Types of microcapsules

6. Formulation considerations Core material: The core material is defined as the specific material to be coated whether it can be a solid or liquid. The solid core can be the active ingredient, stabilizers, diluents, excipients, release rate retardants whereas liquid core include the dissolved materials. Coating material: Coating materials are defined as a layer of substance covered over the core for production of the drug. The coating material should possess properties such as It should have controlled release under specific conditions, soluble in aqueous media/solvent. It should possess sufficient properties such as flexibility, strength, impermeability, stability and optical properties. It should be chemically compatible with the core and non-reactive. It should be capable of forming a film.

7. Water soluble resin Water insoluble resin Wax and lipid Enteric resin Gelatin Ethyl cellulose Paraffin Shellac Gum Arabic Polyethylene Carnauba wax Zein Polyvinyl pyrrolidone Polymethacrylate Bees wax Cellulose acetate phthalate Carboxy methyl cellulose Cellulose nitrate Stearic acid Methyl cellulose Silicones Stearyl alcohol Arabinogalactan Polyvinyl acrylate List of coating materials

8. Core material Characteristic property Purpose of encapsulation Final product form Aspirin Slightly water soluble solid Taste masking; sustained release; reduced gastric irritation, separation of incompatibilities Tablet or capsule Vitamin A palmitate Non volatile liquid Stabilization to oxidation Dry powder Isosorbide dinitrate Water soluble solid Sustained release capsule Properties of some microencapsulated core materials

9. Techniques for preparation of microcapsules Microencapsulation techniques Physical methods Chemical methods Physicochemical methods

10. A. Air suspension coating: In this method the core material which is a solid is dispersed into supporting air stream and these suspended particles of drug coated with polymers in volatile solvent release leaving a very thin layer/film of a polymer on core. The process is repeated for several times until required parameters such as coating thickness are achieved. The air stream which supports particles also helps to dry the particles. The rate of drying is directly proportional to the temperature of air stream. The coating 1. Physical Methods chamber is arranged such that particles move upwards through coating zone, then disperse into moving air and back to the base of coating chamber making repeated passes until desired thickness is achieved.

11. B. Coacervation process: In this process, the core material is dispersed in the solution of coating material such that the Core material doesn’t dissolve/react in solvent. Coacervation occurs when there is a change of pH value of the dispersion which is done either by adding sulphuric acid, Hcl, organic acids as a result it decreases the solubility of the dispersed phase (shell material) and proceeds to form precipitate from the solution. The shell material forms a continuous coating around core and shell cools down to harden and forms a microcapsule. The hardening agents such as formaldehyde may be added to the process. The suspension was then dried in spray drier / fluidized bed dryer.

12. C. Pan coating: It is the one of the oldest method used in pharmaceutical industry. In this method, the particles are tumbled in a pan while the coating material is applied slowly. The solution is applied from the atomized spray to the core material, hot air is passed to remove coating solvent. Particles > 600µm in size are essentially effective for pan coating.

13. D. Spray drying and congealing method: This method is suitable for labile drugs because of less contact time in dryer & it is economical. In this process active material is dissolved/suspended in polymer solution and trapped in the dried particle. Both the methods are similar in process of dispersion of core & coating substance but there is a difference in rate of solidification of coating. In spray drying, there is a rapid evaporation of solvent in which coating material is dissolved whereas in case of spray congealing solidifying occurs by thermal congealing/introducing a non solvent. Removal of non solvent is by sorption, extraction and evaporation. f

14. 2. Chemical Methods Solvent evaporation method: This method is widely used for water soluble and water insoluble materials to produce solid and liquid core materials. A variety of film forming agents or polymers can be used. In this method, the coating material (polymer) is dissolved in a volatile solvent which is immiscible with the liquid vehicle phase. A core material (drug) which is to be microencapsulated is dissolved or dispersed in the coating polymer solution. With agitation, the core coating material mixture or dispersion is dispersed in the liquid manufacturing vehicle phase to obtain the appropriate size microcapsule. The solvent is evaporated either by continuous agitation or by application of external heat supply.

15. 3. Physico-chemical Methods Coacervation phase separation: Coacervation means the separation of a liquid or phase when solution of two hydrophilic colloids are mixed under suitable conditions. In this method, the three immiscible phases of core material, solvent and coating material are formed followed by deposition of coating material on the core. The coating material is dissolved in a suitable solvent and the core material is uniformly dispersed in the solution of the coating material. Then the coating material is phased out of its solution which starts getting deposited on the particles of the core material. Coat formation during coacervation-phase separation process consists of three steps carried out under continues agitation Formation of 3 immiscible phases (core material, coating material phase, liquid phase). Deposition of polymer on core material. Rigorization of coating material.

16. Phase separation can be achieved by- Temperature change Incompatible polymer addition Non-solvent addition Salt addition Polymer-polymer interaction

17. Evaluation of microcapsules Percentage Yield- The total amount of microcapsules obtained was weighed and the percentage yield calculated taking into consideration the weight of the drug and polymer. “Percentage yield = Amount of microcapsule obtained / Theoretical Amount×100 ” Scanning electron microscopy- Scanning electron photomicrographs of drug loaded with polymer, microcapsules were taken. A small amount of microcapsules was spread on gold stub and was placed in the scanning electron microscopy (SEM) chamber. The SEM photomicrographs are taken at the acceleration voltage of 20 KV. Encapsulation efficiency- Encapsulation efficiency was calculated using the formula: “Encapsulation efficiency = Actual Drug Content / Theoretical Drug Content ×100 ”

18. Particle size analysis- For size distribution analysis, different sizes in a batch were separated by sieving by using a set of standard sieves. The amounts retained on different sieves were weighed. Invitro Drug release Studies- Drug release was studied by using USP type II dissolution test apparatus in Phosphate buffer of pH 7.4 (900 ml). The paddle speed at 100 rpm and bath temperature at 37 ± 0.5°c were maintained through out the experiment. A sample of microcapsules was used in each test. Aliquot equal to 5ml of dissolution medium was withdrawn at specific time interval and replaced with fresh medium to maintain sink condition. Sample was filtered through Whatman No. 1 filter paper and after suitable dilution with medium; the absorbance was determined by UV spectrophotometer at specific wavelength. All studies were conducted in triplicate (n=3). The release of drug from marketed sustained release tablet was also studied to compare with release from microcapsules.

19. Applications of microcapsules in pharmacy To improve the flow properties. e.g. Thiamine, Riboflavin To enhance the stability. e.g. Vitamins To avoid incompatibilities. e.g. Aspirin and Chloramphenicol To convert liquids into solids. e.g. Castor oil, Eprazinone To reduce gastric irritation. e.g. Nitrofurantoin, Indomethacin To reduce the volatility of materials. e.g. Peppermint oil, Methyl salicylate To mask the unpleasant taste and odor. e.g. Aminophylline, castor oil Microencapsulation has been employed to provide protection to the core materials against atmospheric effects, e.g., Vitamin A Palmitate. Separation of incompatible substance has been achieved by encapsulation To mask the bitter taste of drugs like Paracetamol, Nitrofurantoin etc. To reduce gastric and other gastro intestinal (G.I) tract irritations, For e.g., sustained release Aspirin preparations have been reported to cause significantly less G.I. bleeding than conventional preparations.

20. A liquid can be converted to a pseudo-solid for easy handling and storage. e.g. Eprazinone. Hygroscopic properties of core materials may be reduced by microencapsulation e.g. Sodium chloride. Carbon tetra chlorides and a number of other substances have been microencapsulated to reduce their odor and volatility To reduce volatility of liquids like peppermint oil Helps to prepare SRDF and enteric coated products, controlled release products Used to improve flow properties before compression into tablets Brand name API Manufacturer ReGel (oncogel) Paclitaxel Macro Med Inc. Clopidogrel Clopidogrel + Aspirin Lupin pinnacle Clobitab Clopidogrel + Aspirin Lupin pinnacle Atoplus Atorvastatin Triton (calyx) Some examples of marketed formulations of microcapsules.