Copolymerized PEGlyated Acrylate Hydrogels for Delivery of Dicolofenac Sodium - Pharmaceutical Technology

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Copolymerized PEGlyated Acrylate Hydrogels for Delivery of Dicolofenac Sodium
Hydrogels are biocompatible drug delivery systems by which the physical properties can be controlled by the cross-linking density. Hydrogels were prepared by copolymerization of acrylic acid monomers in the presence of poly(ethylene glycol)(PEG) to form polyethylene diacrylate (PEDGA). Various molecular weights of PEGs were used for the synthesis of PEGDA to study the effect of molecular weight of PEG on the properties of hydrogels. These hydrogels were further characterized for free water, swelling..

Pharmaceutical Technology

These are copolymers of polyacrylates formed at the terminals of PEGs, which attach to polyacrylates at the other terminal of different PEGs, causing interlinkages because of the nonspecificity of interactions every time. Polyacrylate on one PEG unit always is freely attracted and linked with polyacrylates on other PEG units. This condition causes randomly networked structures. In such copolymeric networks, where instead of traditional low-molecular weight cross-linkers, higher molecular weight PEGs were used. This change caused the simple polyacrylate units to entangle with the PEGs within such structures by acrylate initiators at the terminals. Such results, therefore, can be justified for the equilibrium water content and swelling ratios of hydrogels based on the hydrophilic propensity of such hydrophilic PEGDAs of higher molecular weights as PEGs. PEGDA is hydrophilic, so with the increase in the ratio of PEGDA in copolymeric structures, the hydrophilicity of the hydrogels increased. The hydrophilic nature of PEG decreases with the increase in molecular weight; therefore, the hydrophilicity of these copolymeric hydrogels decreased with the increase in molecular weight. Also, for same weight ratio, the molar percentage of PEGDA decreases with the increase in molecular weight, thereby reducing the hydrophilicity of the polyacrylate gel structures. The PEG present in such polyacrylates decreases with the increase in molecular weights at the same weight percentages. The water absorption inside the gel matrix is lower, so the swelling ratio is less. The diffusivity of water or drying of the hydrogels are at the same time controlled by the presence of PEG, so the diffusion coefficient increased with reduced hydrophilicity of the carriers.

Drug loading . Drug loading can be done either during polymerization (in situ drug loading) or after polymerization by incubating the prepared hydrogels in the drug solution. Exposure to radiation, however, may cause a change in the chemical structure of the drug, if the loading is done during polymerization (5). In the present project, the loading of hydrogels with the drug was performed by equilibrium absorption from the concentrated drug solution.

The hydrogel was filled in a dialysis bag and suspended in a drug-solution of known concentration. The volume of loading solution was kept in excess as compared with the volume of the hydrogel to ensure that the external drug concentration remained relatively constant. After equilibration for 24 h or 48 h as described previously, the hydrogels were dried into glassy, dehydrated drug-loaded hydrogels. A part of the loaded drug might get adsorbed on the surface of the hydrogels, and the rest of the druggets entrapped in the hydrogel matrix.

The drug-loading efficiency was estimated by extracting the loaded drug by methanol. The extraction procedure was repeated a few times with small volumes of methanol to extract the drug completely. The extracts then were pooled and dried. The residue was dissolved in a respective solvent system and analyzed spectrophotometrically against a suitable blank. The hydrogels showed good drug-loading capacity, e.g., formulation B10 contained 67.6% w/w% diclofenac (see Table III). The drug may get released from the pores present in the hydrogels, which can accommodate large amounts of drug molecules.

The drug-loading capacity was higher in hydrogels containing higher amounts of PEG. As the extent of PEGylation decreased with the increase in molecular weight of PEGDA, the entrapment efficiency of the hydrogels decreased, as in the case of B10 having 67.6% w/w entrapment efficiency whereas B60 showed entrapment of 32.1% w/w for diclofenac sodium.

Figure 6
Drug-release profile . The release profiles were determined in distilled water by suspending a dialysis membrane containing the drug-loaded system filled in a 20-mL release medium at neutral pH. The sink condition was maintained continuously by replacing the receptor media each time with fresh fluid after sampling. The cumulative amount of the drug released (expressed as a percentage) after several time-intervals was estimated and plotted against time (see Figure 6).


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