1. SUSPENSIONS

2. SUSPENSIONS are micro heterogeneous dispersion systems consisting from solid medicinal substances in the suspended state, which are in the liquid dispersion medium (water, non-aqueous solvents).

3. Suspensions are liquid medicinal forms containing one or some powdered medicinal substances, as a disperse phase distributed in the liquid dispersion environment.

7. Advantages of suspensions Fast and complete manifestation of the therapeutic action because of the possibility of introducing solid insoluble substances into a liquid where they have a high degree of dispersion ability. Prolongation of the action and the possibility to regulate it duration by changing the particles size of a medicinal substance. The possibility of correcting an unpleasant taste, smell and colour of a medicinal substance due to introduction of correcting agents into the suspension’s composition. Simplicity and convenience of their application in pediatrics and gerontology.

8. Poisonous and strong-effective substances don’t used in suspensions, because difficult to dose of them.

9. Suspensions are formed: when prescribing substances insoluble in the formulated solvent when prescribing soluble substances in amounts exceeding the limit of their solubility in the given solvent a new compound insoluble in the given solvent is formed because of the chemical interaction of solutions with substances when the conditions of substances’ solubility are worsened as the result of mixing two solutions prepared with different solvents

12. STABILIZATION OF SUSPENSIONS To increase of the aggregation stability of suspensions with hydrophobic substances, which do not form protective hydrate layers on the surface, it is necessary to lyophilize them, i.e. to add hydrophilic colloidal substances (stabilizers). Natural or synthetic high- molecular compounds (HMC): proteins, gelatosa, vegetative slime, natural polysaccharide complexes, methylcellulose, sodium - carboxymethylcellulose, polyvinylpyrrolidon, polyglycine, tweens, spens, bentonites, etc. are applied as stabilizers. The stabilization of these substances consists of formation of hydrate layers on the surface of the suspension’s particles, as well as in spanning of these particles by long macromolecules.

13. The amount of a stabilizer for 1.0 g of a hydrophobic substance The name of a stabilizer The amount of a stabilizer per 1.0 g of the substance with distinctly expressed hydrophobic properties: camphor, menthol with poor expressed hydrophobic properties: terpin hydrate, phenylsalicylate, etc. Gelatose 1.00.5 5 % methylcellulose solution 2.01.0 Tween-80 0.20.1

14. METHODS OF PREPARATION SUSPENSIONS Suspensions of medicinal substances are prepared by two methods: Dispersion- The method of obtaining the certain degree of dispersion by powdering dry medicinal substances – Rough suspensions- The method of “making muddy”- for hydrophilic substances with a high density (basic bismuth nitrate)

15. Condensation- The method of formation of large particles from molecules - aggregates, due to the chemical interaction or replacement of a solvent- Thin suspensions- Suspensions are formed: as a result of the chemical interaction; as a result of the solvent’s replacement

16. FORMULATION OF SUSPENSIONS BY THE DISPERSION METHOD Formulation of suspensions with hydrophobic substances Stage I Triturate a dry medicinal substance in the mortar Stage II Triturate (according to the Deryagin rule) with 50% amount of the liquid (add 0.4-0.6 ml of a liquid (40-60%) for 1.0 g of the powdered substance) Stage III Mix and dissolve in water (add water gradually) and transfer into the bottle for dispensing

20. Rp.: Zinci oxydi 10.0 Aquae purificatae 100 ml Misce. Da. Signa. For washes. WCP (front side) Date № Pr. Zinci oxydi 10.0 Aquae purificatae 100 ml m total = 110.0 Prepared by: (Signature) Checked by: (Signature) Weigh 10.0 g of ZnO in the mortar, triturate it, measure 100 ml of the purified water using a cylinder, add approximately 5 ml of the purified water in the mortar according to the Deryagin rule, triturate and then add gradually the remaining quantity of water. Pour the suspension obtained into the bottle for dispensing. Stick the labels «External», «Shake well before use» and «Keep out of the reach of children».

21. FORMULATION OF SUSPENSIONS BY THE DISPERSION METHOD Method of “making muddy” (“shaking”) is applied for preparing suspensions with hydrophilic substances characterized by a great density. Stage I Triturate a solid medicinal substance in the mortar. Stage II Triturate (according to the Deryagin rule) with 50% amount of the liquid calculated by the amount of a dry substance (add 0.4-0.6 ml of a liquid (40-60%) per 1.0 g of the powdered substance). Stage III Add 5-10 % of the liquid to the mixture obtained, triturate, allow to stand for 1-2 minutes. Stage IV When the liquid is settled (the big particles settle at the bottom and the thin particles are on the top of the surface), transfer it into the bottle for dispensing. The stages III-IV are repeated until all precipitate is transferred into a thin dispersed state.

22. Rp.: Bismuthi subnitratis 2.0 Aquae Menthae 200 ml Misce. Da. Signa. 1 tablespoon 3 times a day.

23. FORMULATION OF SUSPENSIONS BY THE DISPERSION METHOD Rp.: Therpini hydrati 2.0 Natrii hydrocarbonatis 1.0 Aquae purificatae 100 ml Misce. Da. Signa. 1 tablespoon 3 times a day.

24. The mixture is a suspension with terpin hydrate, a substance with poor expressed hydrophobic properties. Therefore, the suspension with terpin hydrate differs by the tendency to flocculation and, as a result, the tendency to fast sedimentation. Measure 80 ml of the purified water and 20 ml of the 5% sodium hydrocarbonate solution into the bottle for dispensing. Triturate 2.0 g of terpin hydrate with 10 drops of alcohol (because terpin hydrate is a poorly powdered substance) in the mortar, then add 1.0 g of gelatose and 1.5 ml of the sodium hydrocarbonate solution (according to the Deryagin rule). Mix and triturate all ingredients thoroughly until a homogeneous mixture is obtained. Then add (by small portions) the sodium hydrocarbonate solution, mix and pour the suspension obtained into the bottle for dispensing.

25. WCP (front side) Date № Pr. Aquae purificatae 80 ml Solutionis Natrii hydrocarbonatis 5% 20ml Therpini hydrati 2.0 Gelatosae 1.0 V total = 100 ml Prepared by: (signature) Checked by: (signature)

26. FORMULATION OF SUSPENSIONS BY THE CONDENSION METHOD Rp.: Calcii chloridi 10.0 Natrii hydrocarbonatis 4.0 Aquae purificatae 200 ml Misce. Da. Signa. 1 tablespoon 3 times a day. СаCl2 + 2NaHCO3 = CaCO3 ↓ + H2O + 2NaCl

27. WCP (reverse side) Sol. Calcium chloride 50 % (1:2):10.0  2 = 20 ml Sol. Sodium hydrocarbonate 5 % (1:20):4.0  20 = 80 ml Purified water: 200 - (20+80) = 100 ml At first two solutions - calcium chloride solution and sodium hydrocarbonate solution – should be prepared and then mix these solutions. Measure 100 ml of the purified water into the bottle for dispensing, add 20 ml of 50 % calcium chloride solution and 80 ml of 5 % sodium hydrocarbonate solution.

28. Quality Control of Suspensions The following tests are carried out in the final quality control of suspension: Appearance Color, odor and taste Physical characteristics such as particle size determination and microscopic photography for crystal growth Sedimentation rate and Zeta Potential measurement Sedimentation volume Redispersibility and Centrifugation tests Rheological measurement Stress test pH Freeze-Thaw temperature cycling Compatibility with container and cap liner

29. Ideal Requirements of Packaging Material It should be inert. It should effectively preserve the product from light, air, and other contamination through shelf life. It should be cheap. It should effectively deliver the product without any difficulty.

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