Enhanced Oral Bioavailability of Etodolac by the Liquisolid Compact Technique: Optimisation, In-Vitro and In-Vivo Evaluation.

BACKGROUND: Poor dissolution of Etodolac is one of the major challenges in achieving the desired therapeutic effect in oral therapy. OBJECTIVE: This study aimed to assess the potential of the liquisolid compact technique in increasing the rate of dissolution of Etodolac and thus its bioavailability. METHODS: Liquisolid compacts were prepared using PEG 400, Avicel PH-200 and Aerosil 200 as non-volatile liquid, carrier and coating material, respectively. The optimisation was carried out by applying a 32 full factorial design using Design expert software 11.0.3.0 to examine the effects of independent variables (load factor and carrier: coating ratio) on dependent variables (angle of repose and % cumulative drug release at 30 min [Q _{30 min]). Assessment of bioavailability was based on a pharmacokinetic study on rabbits and pharmacodynamics evaluation on rats, respectively. RESULTS: The formulation M3 was identified as the optimised formulation based on the better flow (lower angle of repose) and a higher rate of dissolution (Q 30 min >95%). The higher dissolution rate could be due to conversion of Etodolac into an amorphous molecularly dispersed state, availability of larger surface area, enhancement of aqueous solubility and enhanced wetting of drug particles. Studies with DSC, XRD, and SEM verified the transformation of Etodolac from crystalline to amorphous state, a key factor responsible for improving the dissolution rate. The pharmacokinetic profile of M3 was prominent, demonstrating higher absorption of Etodolac in comparison to oral suspension and immediate-release conventional tablets in rabbits. Liquisolid formulation exhibited a 27% increment in paw thickness as compared to 57% and 46% increments for oral suspension and immediate-release conventional tablets, respectively, after 7 hrs in the carrageenan-induced paw model in rats. CONCLUSION: The results indicated the liquisolid compact technique to be a promising strategy to enhance the bioavailability of Etodolac.}

Drug carrier systems for solubility enhancement of BCS class II drugs: a critical review.

Poor aqueous solubility impedes a drug's bioavailability and challenges its pharmaceutical development. Pharmaceutical development of drugs with poor water solubility requires the establishment of a suitable formulation layout among various techniques. Various approaches have been investigated extensively to improve the aqueous solubility and poor dissolution rate of BCS class II and IV drugs. In this literature review, novel formulation options, particularly for class II drugs designed for applications such as micronization, self-emulsification, cyclodextrin complexation, co-crystallisation, super critical fluid technology, solubilisation by change in pH, salt formation, co-solvents, melt granulation, and solid dispersion, liposomal/niosomal formulations, are discussed in detail to introduce biopharmaceutical challenges and recent approaches to facilitate more efficient drug formulation and development.

Development and evaluation of sustained release gastroretentive minimatrices for effective treatment of H. pylori infection.

In the present work, sustained release gastroretentive minimatrices of amoxicillin have been designed and optimized using central composite design. Effect of amount of xanthan gum, rate controlling polymers (HPMC K100M CR/PEO coagulant (1:1)), carbopol 974P, and gas generating couple (sodium bicarbonate/citric acid (3:1)) was studied on dependent (response) variables, i.e., buoyancy lag time, drug release at 1 h, time required for 95% drug release, swelling index, and bioadhesive strength. Minimatrices were prepared by non aqueous granulation method using solution of PVP K30 in isopropyl alcohol. All the formulations were found to contain 99.2% to 100.9% of amoxicillin per minimatrix. Optimum formulation (Formulation number AGT09) containing high level of the independent variables was having buoyancy lag time of 7 min and drug release at 1 h was 32.5%. It required 9.39 h for 95% drug release while swelling index and bioadhesive strength were 341 and 17.9 dyn/cm(2), respectively. This formulation was said to be optimum because it has minimum buoyancy lag time, requires maximum time for 95% drug release, and has higher bioadhesive capabilities. In vitro results of an optimized formulation indicate its sustained drug release and gastric retention capability, which may be very useful for effective treatment of H. pylori infection.

Effect of chitosan crosslinking on bitterness of artemether using response surface methodology.

This work examines the influence of various process parameters on artemether entrapped in crosslinked chitosan microparticles for masking bitterness. A central composite design was used to optimize the experimental conditions for bitterness masking. Critical parameters such as the amounts of artemether, chitosan and crosslinking agent have been studied to evaluate how they affect responses such as incorporation efficiency, particle size and drug release at pH 6.8. The desirability function approach has been used to find the best compromise between the experimental results. The optimized microparticles were characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry. Bitterness score was evaluated by human gustatory sensation test. Multiple linear regression analysis revealed that the crosslinking of chitosan significantly affects incorporation efficiency, particle size and drug release at pH 6.8. The bitterness score of microparticles was decreased to 0, compared with 3+ for pure artemether. The proposed method completed masked the bitter taste of artemether.

Design and optimization of mefloquine hydrochloride microparticles for bitter taste masking.

The objective of the present investigation was to reduce the bitterness with improved dissolution, in acidic medium (pH 1.2), of mefloquine hydrochloride (MFL). Microparticles were prepared by coacervation method using Eudragit E (EE) as polymer and sodium hydroxide as precipitant. A 3(2) full factorial design was used for optimization wherein the drug concentration (A) and polymer concentration (B) were selected as independent variables and the bitterness score, particle size and dissolution at various pH were selected as the dependent variables. The desirability function approach has been employed in order to find the best compromise between the different experimental responses. The model is further cross validated for bias. The optimized microparticles were characterized by FT-IR, DSC, XRPD and SEM. Bitterness score was evaluated by human gustatory sensation test. Multiple linear regression analysis revealed that the reduced bitterness of MFL can be obtained by controlling the dissolution of microparticles at pH 6.8 and increasing the EE concentration. The increase in polymer concentration leads to reduction in dissolution of microparticles at pH > 5 due to its insolubility. However the dissolution studies at pH 1.2 demonstrated enhanced dissolution of MFL from microparticles might be due to the high porosity of the microparticles, hydrophilic nature of the EE, and improved wettability, provided by the dissolved EE. The bitterness score of microparticles was decreased to zero compared to 3+ of pure ARM. In conclusion the bitterness of MFL was reduced with improved dissolution at acidic pH.