Biopharmaceutical evaluation of new slow release tablets obtained by hot tableting of coated pellets with tramadol hydrochloride.

This study was aimed at a biopharmaceutical evaluation of a new oral dosage form of tramadol hydrochloride (TH)--slow release tablets obtained by hot tableting of coated pellets, 100 mg (TP), compared to the conventional slow release tablets, Tramal Retard, 100 mg (TR). Both TP and TR formulations showed a similar release profile of TH (f2 was 71) in in vitro release studies. The in vivo study was a two-treatment, two-period, two-sequence, single-oral dose 100 mg, crossover design using rabbit model with the phases separated by a washout period of 14 days. It was shown that the amount of TH absorbed into the systemic circulation is similar for TP and TR (the 90% confidence intervals for the AUC(0-1), AUC(0-infinity) and ratios were 85-122 and 92-107%, respectively). However, after administration of slow release tablets obtained by hot tableting of coated pellets, a prolonged absorption and elimination processes and a smoother and more extended plasma profile of TH were observed. It can be assumed that the use of a new oral dosage form of TH in patients affects the extension of analgesia after single administration of the drug, with its gradual absorption into the systemic circulation.

In vitro - in vivo evaluation of a new oral dosage form of tramadol hydrochloride--controlled-release capsules filled with coated pellets.

The aim of this study was an in vitro - in vivo evaluation of a new oral dosage form of tramadol hydrochloride (TH), controlled-release capsules filled with coated pellets, 100 mg (TC), compared to the sustained release tablets, Tramal Retard, 100 mg (TR). In vitro release study of both formulations showed a similar release profile of TH over 8 h (f2 was 52). In vivo study (single oral, 100 mg dose administration in 8 rabbits) showed that the amount of TH absorbed into the systemic circulation after TC and TR administration was also similar (90% CI for AUC(0-t) and AUC(0-infinity) were 90-124% and 97-109%, respectively). However, a comparison of AUC(0-t) of pharmacokinetics of TC and TR indicates significantly prolonged absorption and elimination processes of TH when the drug is given in controlled-release capsules filled with coated pellets. It was manifested by longer: mean absorption time (p = 0.0016), mean residence time (p = 0.0268), absorption half-life (p = 0.0016), elimination half-life (p = 0.0493) and lower: absorption rate constant (p = 0.0016), elimination rate constant (p = 0.0148) and total body clearance Cl/F (p = 0.0076). It may be concluded that the new TH formulation could be expected to have a more prolonged analgesic activity than commercial sustained release tablets.

Release characteristics of quetiapine fumarate extended release tablets under biorelevant stress test conditions.

The aim of the present work was the investigation of robustness and reliability of drug release from 50 to 400 mg quetiapine extended release HPMC matrix tablets towards mechanical stresses of biorelevant intensity. The tests were performed under standard conditions (USP apparatus II) as well as under simulated gastrointestinal stress conditions. Mechanical stresses including pressure and agitation were applied by using the biorelevant dissolution stress test apparatus as it has been introduced recently. Test algorithms already established in previous studies were applied to simulate fasting gastrointestinal conditions. The dissolution experiments demonstrated striking differences in the product performance among standard and stress test conditions as well as dose strengths. In USP apparatus II, dissolution profiles were affected mainly by media pH. The dissolution experiments performed in biorelevant dissolution stress test device demonstrated that stress events of biorelevant intensity provoked accelerated drug release from the tablets.

Hot tabletting of slow-release tramadol hydrochloride microcapsules with cores obtained via compaction.

BACKGROUND: Coating, as a processing technique, applied to active pharmaceutical ingredient (API) crystals or particles (carriers) with an appropriate polymer allows to obtain a modified-release pharmaceutical dosage form. Such carriers can be the basic ingredient of a multi-unit dosage form. Additionally, coated API crystals (microcapsules) can provide an alternative to spherical granulate (pellets) as the main and most commonly used component of multi-unit dosage forms. Coating individual API crystals is a complicated process because of the crystals having insufficient size (below 100 microm), irregular shape, low mechanical durability and the fact that API crystals dissolve upon contact with the coating mixture, and other factors. METHOD: Compaction process was used to eliminate these inconveniences allowing us to obtain tramadol hydrochloride (TH) microcapsule cores in the size range of 212-500 microm. The coating of the cores was successfully conducted using a fluidized-bed coating technique with four different polymers that allowed us to attain slow release of TH. Then, the microcapsules were subjected to a hot tabletting process conducted by applying a low compression force of about 1 kN at 56 degrees C. Semi-liquid granules containing melted PEG 3000 combined with TH microcapsules were compressed. A tablet matrix of good physical parameters was created when its temperature decreased to room temperature. In the proposed hot tabletting method, PEG 3000 included in the granulate provided the tableted microcapsules sufficient protection against rupture. RESULTS: The compaction process allowed us to eliminate unwanted physical API properties, which could otherwise have an adverse effect on the fluidized-bed coating process. The microcapsule cores after compaction and coating using a fluidized-bed coating technique showed a TH-release profile similar to that of the compressed microcapsules after applying hot tabletting process. CONCLUSIONS: Multi-unit dosage forms can be obtained in a relatively simple way by combining three processes: (i) obtaining TH microcapsule cores by compaction, (ii) coating, and (iii) hot tabletting.

Hot tableting as a new method for obtaining tablets from slow release-coated pellets.

BACKGROUND: Coating of pellets poses difficulties in the tableting process, which is attributed to the fact that ethylcellulose is a fragile polymer having low resistance to compression. This property of ethylcellulose is the reason why obtaining a slow release profile from tableted pellets comparable with that of uncompressed pellets is practically impossible when traditional tableting process is employed. METHOD: This work presents a newly developed method of hot tableting of pellets. The pellets used in the process were tramadol hydrochloride (TH) coated with an Aquacoat ECD aqueous dispersion. A physical property of PEG 3000 (one of the components of the tablet formulation) to liquidify at a given temperature was used in the process of hot tableting carried out at about 56 degrees C. RESULTS: During the hot tableting, when a low compression force of about 1 kN was applied, semiliquid granules containing melted PEG 3000 combined with TH pellets. As the temperature decreases to room temperature, a tablet matrix of good physical parameters was created. In the proposed hot tableting method, granulates containing PEG 3000 provide the tableted pellets sufficient protection from being destroyed. An evidence of such protection is confirmed by the fact that the TH slow release profile from the tableted pellets is comparable to that of uncompressed pellets. CONCLUSION: The hot tableting method allows to obtain the tablets containing compressed pellets with a TH slow release profile comparable to that of uncompresed pellets.