Formulation and in-vivo study of ketoprofen tablets prepared using chitos an interpol ymer complexes

The application of interpolymer complexes [IPCs] for oral controlled drug delivery systems was tested between chitosan and various anionic polymers viz sodium alginate, sodium carboxymethylcellulose and pectin. The prepared IPCs were investigated using Fourier transform infra-red spectroscopy and differential scanning calorimetry, Ketoprofen tablets were prepared using the polymers alone, physical mixtures of chitosan with sodium alginate, sodium carboxymethylcellulose or pectin in different ratios; 1:3, 1:1 and 3:1, and the corresponding IPCs. In-vitro release studies were carried out in two dissolution media; 0.1 N HCl ofpH 1.2 and phosphate buffer ofpH 7. 4. It was found that, chitosan - sod. carboxymethylcellulose 1PC tablets showed more controlled drug release compared to that containing chitosan - sodium alginate and chitosan -pectin IPCs. The dissolution rate from tablets prepared using physical mixtures of polymers were found to be dependant on the interaction between chitosan and each of the anionic polymers in the physical mixtures, their ratios and pH of the dissolution medium. Tablets prepared using chitosan - sod. carboxymethylcellulose physical mixture 1:1 and chitosan - sod. carboxymethylcellulose IPC were selected for the in-vivo study using albino rabbits. The results showed a lower peak plasma concentration and marked controlled release effect of drug in tablets containing the physical mixture compared to that of the IPC and the control tablets

Formulation and evaluation of a buccoadhesive captopril tablets

Buccoadhesive tablets of captopril were prepared by direct compression of the drug with different polymers; Carbopol 934 [CP 934], EudragitRS 100 [EU RS 100], Chitosan [Ch], Hydroxpropyl methylcellulose [HPMC] and Polyvinylpyrrolidone K[30] [PVP K[30]] either singly or in blends of different ratios. The tablets were evaluated for their weight variation, drug content uniformity, friability, hardness, swelling index, surface pH, in-vitro bioadhesive strength and release characteristics. The bioavailability and the pharmacokinetics parameters of captopril from two selected formulations [CP 934:HPMC 6:4 andCh:HPMC 6:4] were evaluated. The in-vitro bioadhesive strength and release characteristics were found to be a function of the type of polymer and ratio of polymer blends. Swelling and bioadhesive characteristics were determined for both plain and medicated tablets. The high concentration of carbopol and chitosan containing formulations showed the greatest adhesive strength. The mean pharmacokinetic parameters of captopril after buccoadhesive tablet administration were: C[max] 506.9 ng/ml, T[max] 4 hr, AUC[0-8] 2359.5 ng.hr/mlfor CP 934: HPMC [6:4], while C[max] 429.02 ng/ml, T[max] 2.67 hr, AUC[0-8] 1637.43 ng.hr/ml for Chitosan: HPMC [6:4]. In comparison, in case of oral administration of control tablet the C[max] 591.28 ng/ml, T[max] 1.5 hr, AUC[0-8] 1869.29ng.hr/ml

effect of binder type and major diluent on the migration and bioavailability of riboflavin sodium phosphate during tablet making

The migration of riboflavin sodium phosphate [RSP] upon drying of its wet granules was studied through the formulation of granules using different diluents [lactose monohydrate and anhydrous dibasic calcium phosphate], different binders of different concentrations; polyvinyl pyrrolidone [PVP k[25]], methylcellulose [MC], hydroxypropylmethyl cellulose [HPMC] and gelatin at different drying temperatures [50°C and 70°C]. The prepared granules were compressed into tablets and evaluated. In vitro drug release from the formulated tablets was performed. In addition, in vivo study was conducted on some selected tablet batches. The results showed that, the granules prepared with dibasic calcium phosphate showed lower migration for the drug than those prepared with lactose. Also, drug migration decreased with increasing the binder concentration and viscosity. The degree of tablet mottling was inversely proportional to the binder concentration. Tablets prepared with 10% w/w gelatin were found to be the least mottled ones. In addition, they showed the least friability percentage, the highest hardness value and the highest disintegration time. Tablets prepared with 0.5% MC showed the highest dissolution rate, however, those prepared with 10% gelatin had the lowest dissolution rate. Generally, increasing the binder concentration resulted in slowing the in vitro drug release from tablets. The in vivo study showed that, tablets prepared with 10% w/w gelatin showed the lowest excretion rate and the highest T[max] [1.5 hours]. Meanwhile, tablets prepared using 0.5% w/w MC exhibited higher excretion rate and T[max] of 0.5 hour

Bioavailability and ocular disposition of ketorolac tromethamine from various ophthalmic preparations

Ketorolac tromethamine was formulated in different ophthalmic preparations namely; eye drops, gels, ocuserts and ointments using the following carriers; sodium carboxymethyl cellulose [sod. CMC], polyvinyl alcohol [PVA], hydroxypropylmethyl cellulose [HPMC], absorption base and gelatin. The ophthalmic formulations were prepared containing 0.5% of the drug. All prepared formulae containing the drug were subjected to stability study and release characteristics. Also, the effect of these drug carriers on the uptake and ocular disposition of ketorolac tromethamine by the eye tissues of rabbits [conjunctiva, cornea, iris-ciliary body and aqueous humor] was studied. The obtained results revealed that, the released amounts from the ophthalmic preparations after six hours can be arranged in the following order; Eye drops > ocuserts > gel > ointments. Sod CMC eye drops exhibited the higher rate of release than sod CMC gel, PVA and absorption base ointments. Gelatin ocuserts exhibited the higher rate of release than HPMC ocuserts and carbopol 934 and sod CMC ocuserts. The release rate of the drug from eye drops and PVA ointment obeys first order kinetics, while, other preparations obey Higuchi diffusion model with non-Fickian kinetics. Most formulations [including eye drops] could be stored for 6 months at 25°C, 35°C, 45°C without physical or chemical degradations of the drug. However, PVA and absorption bases showed some changes in the drug content [t[90] was 2.84 months for both at 45°C]. The decomposition rate ofketorolac tromethamine followed the first-order degradation kinetic. The highest stable formulae are, sod CMC eye drops and gel [t[90] values were, 151.9 and 91,18 months, respectively at 45°C]. The highest concentration of the drug [Cmax] from all tested formulations is provided in conjunctiva followed by cornea, iris-ciliary body, then aqueous humor. The peak time for maximum drug concentration [Tmax] from sod CMC eye drops was two hours. While, that for sod CMC gel, PVA ointment and gelatin ocuserts was three hours in all tissues after the application of the tested formulations. In addition, the total availability of the drug from the tested formulations was in the following order: gelatin ocuserts > sod CMC gel > PVA ointment > sod. CMC eye drops

Formulation and stability study of naproxen ophthalmic preparations

Naproxen was formulated in different ophthalmic preparations as drops, gels and ocuserts using cellulose derivatives such as methylcellulose, sodium carboxymethylcel-lulose and hydroxypropyl methylcellulose. All the prepared formulae [drops, gels and ocuserts] containing the drug were subjected to the study of the release characteristics. Also, the stability of naproxen ophthalmic preparations at different conditions of storage were investigated. The obtained results revealed that, the percentage released of naproxen from the three ophthalmic dosage forms after 7 hours were found to be in the following order; Drops>ocuserts>gels. These formulations exhibited the highest physical and chemical stability up to 6 months of storage at 25°C, 35°C and 45°C, except the formulae containing methylcellulose polymer, showed the least stable formulations. The drug content in the formulae containing methylcellulose was decreased about 10% after storage at different temperatures for 6 months

In-vitro evaluation of enrofloxacin ophthalmic preparation containing cyclodextrins

The effects of cyclodextrins [CyDs] [hydroxy propyl beta-cyclodextrin [HP-beta-CyD] and beta-cyclodextrin [beta-CyD]] on the solubility and release characteristics of enrofloxacin [Enr] from ophthalmic ointments and gels were investigated. The ophthalmic gels [sodium carboxymethyl cellulose [sod. CMC] and sodium alginate] and ointments [emulsion, absorption and water soluble bases] were prepared using 0.5% of the drug or equivalent amounts of its complexes with HP-beta-CyD or beta-CyD. The results revealed that the aqueous solubility of enrofloxacin was significantly increased by the formation of [1:2] inclusion complexes with CyDs. However, the solubility of enrofloxacin increased linearly as a function of HP-beta-CyD, followed by beta-CyD

Effect of base type and volatile oils on the transdermal delivery characteristics of captopril

In this study, different topical formulations using oleaginous, emulsion and water soluble bases containing 1% [w/w] captopril were prepared by the fusion method. The penetration behavior of captopril from these preparations was studied through excised rabbit skin. The influence of the base type as well as some of the volatile oils on the mechanism and transdermal delivery characteristics of the drug was investigated. At the end of experiments, the percentages of the drug transported were 89.66, 83.18 and 63.87 from emulsion, oleaginous and water soluble bases, respectively. The addition of volatile oils to the oleaginous base delayed the transport of the drug in the following order of magnitude: Thymol < menthol < methyl salicylate < cinnamaldhyde < camphor. This inhibition was significant in case of alcoholic [menthol] and phenolic [thymol] monoterpenes, whereas other oils exhibited no significant effect

pH-independent controlled release tablets comprising weakly acidic drug: design and evaluation

In this study, tablets were prepared by compressing mixtures of indomethacin [model drug], PVP and tromethamine [as an alkalinizer] in order to attain independent release pattern. The tablets were coated with 5% ethyl cellulose in ethyl acetate on the lateral site leaving two surfaces free or coated at all surfaces, except one. When the composition of tromethamine to the drug in the mixture was equal to or more than 4.5:1, the tablets showed pH-independent release. Release rate was controlled with tromethamine/drug ratio, the percent and type of PVP and the surface area available for drug release. Release rate can be altered freely, while maintaining the pH-independent release characteristics by combining the different composition matrices. The study showed that the best model to describe indomethacin release kinetics is mixed zero-order and Higuchi linear square root of time relationships with lag time

Ibuprofen-quercetin combination as a novel pharmaceutical compatible system

The effect of oral administration of quercetin [QRT] [25 mg/kg] on an experimentally Ibuprofen-induced ulcer was studied in rats. The results of gross appearance and scanning electromicrographs of the mucous membrane and superficial cells of the stomach revealed that the quercetin reduced the damage of submucosal superficial cells. Differential scanning calorimetry, X-ray diffractometer, IR spectroscopy, solubility and partitioning studies elucidated the absence of any interaction between the two compounds and also the physical compatibility of ibuprofen [IP]-quercetin combination. It is concluded that ibuprofen and quercetin can be pharmaceutically co-formulated or co-administrated with the aim of reducing the gastrointestinal adverse effects of ibuprofen