Semi Solid Dosage form PDF

‫رلبلنللا م هللا مسب‬ Semi solid Dosage form GEL Deina Elraiah Mohamed El Hassan Master degree of Pharmaceutical Technology (University of Gezira) PhD holder of Pharmaceutical Technology (Karary University)  ???????????? What is diff...

‫رلبلنللا م هللا مسب‬ Semi solid Dosage form GEL Deina Elraiah Mohamed El Hassan Master degree of Pharmaceutical Technology (University of Gezira) PhD holder of Pharmaceutical Technology (Karary University)  ???????????? What is difference of ointment and paste? Mention 2 types of ointment? What is main types of the base used for ointment? How to select the ointment base? Define the components of the emulsifing wax?  Pharmaceutical Gels Definition Gels are usually homogeneous, clear, semi-solid preparations consisting of a liquid phase within a three-dimensional polymeric matrix with physical or chemical cross-linkage by means of suitable gelling agents. Or Gels In Pharmaceuticals are usually consisting of solutions or dispersion of one or more medicaments in suitable hydrophobic and hydrophilic bases.  Antioxidants, Preservatives, and stabilizers, gelling agent may be added to the gels. Gelling agents are the gel-forming agents when dissolved in a liquid phase as a colloidal mixture forms a weakly cohesive internal structure and enhance the thickness or viscosity of the formulation Gels applied for large open wounds, and severely injured skin shall be sterile and applied to the skin or certain mucous membranes for protective, therapeutic, or prophylactic purposes. Types of gels based on vehicles : 1. Hydrophobic gels Hydrophobic gel (oleogel) bases usually consist of liquid paraffin with polyethylene or fatty oils gelled with colloidal silica or aluminium or zinc soaps. 2. Hydrophilic gels Hydrophilic gel (hydrogel) bases usually consist of water, glycerol, or propylene glycol gelled with suitable agents such as tragacanth, starch, cellulose derivatives, carboxyvinyl polymers, and magnesium aluminium silicates.  There are two main categories of pharmaceutical gels, based on the nature of the three-dimensional network of particles: (1)Dispersed solids (2) Hydrophilic polymers. Gels based on dispersed solids Gels like suspensions in which thermodynamically a disperse system may be considered to be stable whenever there is no interaction between particles(secondary minimum region where attractive forces predominate). Particles located at the secondary minimum are termed floccules, this process being termed flocculation. This interaction increases the physical stability of the dispersion by preventing the close approach to the primary minimum.  If flocculation extends throughout the system a continuous solid particle network is established, with the liquid vehicle dispersed in the void volume between the particles. However, for certain dispersed solids the nature of the interaction is electrostatic bonding. Examples of the particles that exhibit this type of interaction include kaolin, bentonite and aluminium magnesium silicate. The particles exhibit a plate-like crystal structure in which there are electronegative regions along the flat face of the crystal (due to O–) and electropositive regions (due to the ionised aluminium and magnesium ions) at the edges of the plates.  The interaction of these two regions facilitates the establishment of a structured ‘house of cards’-type particle network.  The bond strength between the particles is weak interparticle bonds are broken by the application of relatively low shearing stresses (shaken), thereby liberating the individual particles. Following removal of the stress the bonds between the particles will reform. This time- dependent recovery of the rheological structure is termed thixotropy. Gels based on hydrophilic polymers Pharmaceutical gels are most commonly (but not exclusively) manufactured by dispersing hydrophilic polymers within an appropriate aqueous vehicle. When dissolved within an aqueous phase, hydrophilic polymers behave as lyophilic colloids and their unique physical properties result from the self-association of the dissolved polymer and its interaction with the aqueous medium.  There are two types of self-association (termed irreversible and reversible) that may be demonstrated by lyophilic colloids and this allows gels that are manufactured from lyophilic colloids to be classified as either üType 1 gels or ü Type 2 gels. Type 1 gels In type 1 gels (hydrogels) the interaction between the polymer chains is covalent and is mediated by molecules that cross-link the adjacent chains (termed cross-linkers), ability to absorb a considerable mass of aqueous fluid, not exhibit flow when exposed to an applied stress due to the inability of the stress to overcome(destroy) the covalent bonds. Hydrogels are clinically used as wound dressings, as lubricious coatings on catheters and as soft contact lenses. In addition, hydrogels may be used for the controlled delivery of therapeutic agents at the site of implantation. Type 2 gels In type 2 gels the interactions between the polymer chains are reversible and are facilitated by weaker bonds, e.g. hydrogen bonding, ionic association or van der Waals interactions. The application of stresses to type 2 gels will end in the temporary destruction of these bonds, thereby enabling the formulation to flow. As a result, type 2 gels are rheologically referred to as pseudoplastic (shear-thinning)systems. Following the removal of the stress, the inter macromolecular bonds are reformed and the viscosity of the formulation returns to its equilibrium value. The majority of pharmaceutical gels are type 2 gels and typically the following polymers are employed in the formulation of these systems Factors affecting gelation of type 2 gels 1. Concentration of hydrophilic polymer At low concentrations, solutions of hydrophilic polymers exhibit Newtonian flow due to the limited number of polymer–polymer interactions. As the concentration of polymer increases, and increase in the number of junction zones become non-Newtonian (termed the gel point). 2. Molecular weight of the polymer 3. Nature of the solvent. The viscosity of a polymer solution is dependent on the expansion of the polymer chains. 4. PH of the solvent In the non-ionised state acidic and basic polymers exist in a coiled (non-expanded) state and gelation does not occur. 5. Ionic strength of the solvent phase At high concentrations of electrolytes (and hence large ionic strength), non-ionic polymers may be ‘salted out’ of solution due to desolvation of the polymer chains.  Conversely, at lower concentrations of electrolyte, shielding of the charge on the suspended groups of the ionic polymer by a counterion will occur. 6. Temperature Certain hydrophilic polymers may undergo a thermally induced transition that results in an increase in the rheological properties. gelation at elevated temperatures (circa 50–60 ◦C) a) methylcellulose. b) hydroxypropylcellulose c)poly(oxyethylene)-poly(oxypropylene) block co-polymers ( Pluronic (37○C)) undergoes a thermal transition within a biologically useful temperature range (≤ 37◦C). At temperatures below this (sol–gel) transition temperature ( Tsol/gel),solutions of this polymer exhibit Newtonian flow and low viscosity (the sol state). Conversely, above Tsol/gel the polymer sol is converted into a gel with marked elasticity and viscosity. The ability to change the rheological structure of these gels in the manner described has led to an interest in their use as drug delivery systems within the oral cavity and rectum. 7. Ionic gelation Certain hydrophilic polymers may undergo gelation in the presence of inorganic metal ions. Examples of these include: The gelation of polyhydroxypolymers, e.g. poly(vinyl alcohol) may occur in the presence of suitable anions, e.g. borate, permanganate. Interaction between borate anions and poly(vinyl alcohol) that leads to gel formation through borate anion-mediated cross- links. Formulation considerations for pharmaceutical gels There are several formulation considerations open to the pharmaceutical scientist concerning the formulation of pharmaceutical gels. These include: (1) Choice of vehicle; (2)The inclusion of buffers; (3) Preservatives; (4) Antioxidants; (5)Flavours/sweetening agents; and (6) Colours. Manufacture of pharmaceutical gels In the manufacture of pharmaceutical gels, generally the water soluble components/excipients are initially dissolved in the vehicle in a mixing vessel with mechanical stirring. The hydrophilic polymer must be added to the stirred mixture slowly to prevent aggregation and stirring is continued until dissolution of the polymer has occurred. It should be noted that excessive stirring of pharmaceutical gels results in entrapment of air. Therefore, to prevent this the mixing rate must not be excessive or a mixing vessel may be used to which a vacuum may be pulled, thereby removing air. Aggregation Gelatin Drying