The influence of process variables of preparation of oxycellulose beads on their dissolution profile.

Particles preparation from biodegradable polymers as carriers for the controlled release of drugs has been the focus of many investigations and the subject of a growing field of research in recent years. The aim of this study was to develop and optimize the preparation of oxycellulose beads containing diclofenac sodium as a model drug. Particle size, surface, drug content and encapsulation efficiency were evaluated, drug dissolution profiles were measured and drug release mechanism estimated. The prepared oxycellulose beads were uniform in size with encapsulation efficiency ranging from 53.2 to 74.9%. The lower temperature of the crosslinking solution and its saturation with diclofenac sodium increased the encapsulation efficiency, especially when both parameters were combined. The application of ultrasound had a negative effect on drug encapsulation. The dissolution of diclofenac sodium in pH 1.2 was close to zero as its solubility in this medium is very limited. The drug release in pH 6.8 lasted from 10 to 16 h showing biphasic behavior with a significant lag time. T1/2 decreased with increasing encapsulation efficiency and ultrasound application. Diclofenac sodium was released from the prepared oxycellulose particles by diffusion as well as by erosion process; ahigh correlation was found with zero order kinetics.

The development of Eudragit® NM-based controlled-release matrix tablets.

UNLABELLED: Eudragit® NM was investigated as a matrix former in combination with microcrystalline cellulose as an insoluble filler for preparing controlled-release tablets containing model drugs with different solubility. MATERIAL AND METHODS: Three sets of matrix tablets differing in the drug-to-filler ratio (1:1, 2:1, and 4:1) and polymer amount with diltiazem hydrochloride (freely soluble) or caffeine (sparingly soluble) were prepared. Samples were evaluated by the dissolution test at pH 6.8 corresponding to the upper part of the small intestine; the selected samples were tested at a changing pH level to better simulate in vivo conditions. RESULTS: The prepared matrix tablets fulfilled all the requirements of the European Pharmacopoeia. Tablets with Eudragit® NM showed excellent mechanical characteristics. In vitro studies showed that the set 1:1 was the most suitable for the sustained release of a freely soluble drug concerning the burst effect and the total drug amount released within 12 hours. The significant effect of the drug-to-filler ratio and polymer amount on the dissolution profile was confirmed by similarity factor analysis. A faster drug release was observed during the dissolution test within changing pH levels because of the pH-dependent solubility of diltiazem. A prolonged release of the sparingly soluble drug was not achieved, and a trend for fast disintegration was observed. CONCLUSIONS: The combination of Eudragit®NM with microcrystalline cellulose as an insoluble filler seems to be suitable only for freely soluble drugs, when the amount of the drug and the filler is similar.

Oxycellulose beads with drug exhibiting pH-dependent solubility.

The aim of this study was to develop novel hydrogel-based beads and characterize their potential to deliver and release a drug exhibiting pH-dependent solubility into distal parts of gastrointestinal (GI) tract. Oxycellulose beads containing diclofenac sodium as a model drug were prepared by the ionotropic external gelation technique using calcium chloride solution as the cross-linking medium. Resulting beads were characterized in terms of particle shape and size, encapsulation efficacy, swelling ability and in vitro drug release. Also, potential drug-polymer interactions were evaluated using Fourier transform infrared spectroscopy. The particle size was found to be 0.92-0.96 mm for inactive (oxycellulose only) and 1.47-1.60 mm for active (oxycellulose-diclofenac sodium) beads, respectively. In all cases, the sphericity factor was between 0.70 and 0.81 with higher values observed for samples containing higher polymer and drug concentrations. The swelling of inactive beads was found to be strongly influenced by the pH and composition (i.e. Na(+) concentration) of the selected media (simulated gastric fluid vs. phosphate buffer pH 6.8). The encapsulation efficiency of the prepared particles ranged from 58% to 65%. Results of dissolution tests showed that the drug loading inside of the particles influenced the rate of its release. In general, prepared particles were able to release the drug within 12-16 h after a lag time of 4 h. Fickian diffusion was found as the predominant drug release mechanism. Thus, this novel particulate system showed a good potential to deliver drugs specifically to the distal parts of the human GI tract.

Coated hard capsules as the pH-dependent drug transport systems to ileo-colonic compartment.

PURPOSE: The aim of this study was to investigate the suitability of hard capsules of different composition (gelatin-G, gelatin coated with hydroxypropyl cellulose-G/HPC, and hypromellose-H) for a coating with aqueous dispersion of pH-dependent synthetic polymer Eudragit(®) FS (E(FS)) and to evaluate in vitro the coated capsules as transport systems for ileo-colonic drug delivery. METHODS: Three sets of hard capsules with increasing coating levels (5-30%) were obtained by Wurster technique. The release of model drug (caffeine) from prepared samples was tested using paddle dissolution method with continual pH change (pH 1.2-2 h, 6.8-4 h and 7.5-2 h). RESULTS: During the coating process, no problems occurred and similar suitability of capsules materials for E(FS) application was observed in contrast to some published reports. The application of HPC subcoating onto gelatin capsules surface was shown as the redundant step. The samples G/E(FS)10-15% and H/E(FS)15-20% with 6 h lag time and fast drug release after the pH adjustment to 7.5 corresponded with the requirements for ileic drug delivery. Samples releasing the drug after the pH change to 7.5 in 2-h interval such as G/E(FS) 20%, G/HPC/E(FS) 25% and H/E(FS) 25% are considered as promising transport systems to ileo-colonic area. Samples G/E(FS) 25-30%, G/HPC/E(FS) 30% and H/E(FS) 30% with 7 h lag time could be used for colon delivery. CONCLUSION: The desired intestinal part could be targeted without significant formulation changes only by the selection of capsules shell forming material and suitable E(FS) coating thickness.

Oxycellulose as mucoadhesive polymer in buccal tablets.

BACKGROUND: Oxycellulose (OC) is biodegradable and bioabsorbable cellulose derivative used in medicine to support hemostasis and tissue healing. Recently, its antimicrobial and immunomodulating properties, as well as its potential in modern therapeutic systems as release modifying excipient, drug carrier, and/or mucoadhesive polymer, are widely discussed. METHOD: To study its last-mentioned characteristics, directly compressed tablets containing 5 mg of cetylpyridinium chloride (CPC) as a model drug and 90 mg of mucoadhesive polymer [oxycellulose sodium (NaOC) alone or in a combination with one of five widely used mucoadhesive polymers] were prepared to ensure 8 hours prolonged release of CPC. Physicochemical and mucoadhesive properties of prepared tablets were evaluated. RESULTS: Based on obtained results, tablets containing OC in combination with hydroxypropylmethylcellulose (Methocel K100LV) or carboxymethylcellulose sodium showed the best quality parameters (friability < 0.04%, tablet thickness < 2.17 mm, tablet hardness > 85 N, residence time > 256 minutes, mucoadhesive strength > 3.45 mN/mm(2) ) and dissolution profiles (more than 81% of CPC released within 8 hours). CONCLUSION: NaOC embodies excellent compressing, mechanical, and mucoadhesive properties; however, formulation with higher content of NaOC only showed shorter adhesion time (107 +/- 7 minutes) and faster drug release (93.66% of CPC released within 2 hours), because of its good solubility in aqueous media.

Coated capsules for drug targeting to proximal and distal part of human intestine.

Coated hard capsules are becoming increasingly important for a number of reasons such as administration of new active ingredients, oral vaccination, colon drug delivery or their use in preclinical and clinical trials. The independency of coating composition on capsules filling is the major advantage of this dosage form. In our study, two types of hard capsules (gelatin and hypromellose) were coated by non-aqueous solutions of Eudragit L and S 12.5, respectively, to achieve intestinal and distal ileic drug delivery. Gelatin hard capsules were coated with Eudragit film either directly or using hydroxypropyl cellulose sub-coating prior to the final coating. Hypromellose capsules were coated directly. Coated capsules were evaluated for coating thickness by optical microscope and for dissolution in different pH media. Gelatin capsules do not seem to be suitable for direct coating with Eudragit due to insufficient film adhesion to the smooth capsule surface and a brittleness of formed films. These problems can be solved by hydroxypropyl celullose interlayer application. Hypromellose hard capsules could be directly easily coated with both Eudragit solutions. Dissolution of caffeine from coated capsules showed the potency for enteric delivery in gelatin capsules with interlayer and Eudragit L film in 7.5 and 10.0% concentrations and in hypromellose capsules coated with EudragitL in 5-17.5% coating levels. Gelatine capsules with interlayer and 10% Eudragit S film and hypromellose capsules only with high coating level (20%) provided potential distal ileum targeting of incorporated drug. Eudragit S film sprayed onto hypromellose capsules surface was brittle especially in the junction zone between capsule cap and body. Better plasticity of Eudragit S coating could be probably achieved using a different plasticizer.