PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Tablets”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 451 records · Page 25Linked to original sources

[Tablet splitting].

The splitting of scored tablets provides many advantages. One benefit is to achieve dose flexibility to account for the huge interindividual differences in dose requirements for instance in paediatric and geriatric patients, which are often not covered by the available strengths in the market. Moreover, large-sized tablets can easier be swallowed if broken before swallowing and medication costs can often be reduced by splitting brands with higher strength. But not all tablets, mostly unscored tablets, are suitable for splitting. Splitting of extended release formulations can result in an overdose by uncontrolled release of the active component and degradation of the compound can occur if an enteric coating is destroyed by the splitting process. Whether tablets are suitable for splitting depends on the properties of the active component (e.g. light sensitivity), the galenics, the shape of the tablet, and the shape of the scoreline. Moreover, not all patients are informed, able, or willing to split tablets and the majority of the elderly population is not capable to break tablets. When split tablets are prescribed it is therefore important to view the shape of the tablet, to assess the patients ability and willingness to break tablets, to properly inform the patient about the appropriate way of splitting, and if necessary to suggest (and instruct) the use of a tablet splitting device.

Drug Administration Schedule↗

The content of ecstasy tablets: implications for the study of their long-term effects.

AIMS: To examine the variation in the content of ecstasy tablets seized in the north-west of England during 2001 and to compare it to the UK average from 1991 to 2001. MEASUREMENTS: All tablets submitted to the Forensic Science Service in the north-west of England during 2001 were analysed by high performance liquid chromatography with diode array detection (HPLC-DAD). The mean MDMA content of these tablets are reported and compared to results from all Forensic Science Service laboratories in the United Kingdom from 1991 to 2001. Multiple samples (n= 80) from a single large seizure of White Dove tablets were analysed to determine the variation due to manufacturing. FINDINGS: All tablets submitted from the north-west of England to the Forensic Science Service in 2001 were found to contain 3,4-methylenedioxymethamphetamine (MDMA) and some also contained 3,4-methylenedioxyethamphetamine (MDEA). The MDMA content of these tablets ranged from 20 to 109 mg and the mean was in the 60-69 mg range. Mitsubishi tablets were the most common type and they were found across the whole range. The low variation of MDMA content in the White Dove tablets suggests that these tablets were well manufactured. The data from the north-west of England in 2001 are in agreement with tablet analyses over the past 10 years which show that the average MDMA content is falling. CONCLUSIONS: The amount of MDMA in ecstasy tablets is axiomatic to the discussion of their long-term effects. In order for the observed differences in ecstasy users to be the result of MDMA-induced neurotoxicity it is necessary for them to have ingested one or more neurotoxic doses. These data indicate that the amount of MDMA in ecstasy tablets is dropping and that dose-effect relationships need to take this into account.

Chromatography, High Pressure Liquid↗

Effect of packaging and storage on the stability of carbamazepine tablets.

The effect of packaging and storage on carbamazepine (CBZ) tablets was examined using Tegretol and Tegral, dispensed in strip seals, and Finlepsin, dispensed in bottles. Tegretol and Tegral tablets were stored in their original strips at 40 degrees C, 50 degrees C, and 60 degrees C for 6 months, 3 months, and 1 month, respectively, at 75% relative humidity (RH). Also, tablets were removed from their strips, placed in bottles, and exposed daily to 97% RH at 40 degrees C for 5 min for 30 days. Finlepsin tablets were exposed to 97% RH at 25 degrees C or 40 degrees C for 1 month by removing bottle caps daily for 5 min. Dissolution was used to assess in vitro tablet performance, and high-performance liquid chromatography (HPLC) was used to evaluate the chemical stability of CBZ. Results show that Tegretol tablets were not affected by the tested stress conditions. Tegral tablets, stored in their strips at 50 degrees C or 60 degrees C and 75% RH, showed increased disintegration and dissolution. The effect of 40 degrees C/75% RH for 6 months was similar to 1-month storage at 40 degrees C/97% RH; the tablets hardened and dissolved less than fresh Tegral tablets. Removal of Tegral tablets from their original strips resulted in only 7% dissolved in 60 min. For Finlepsin, the effect of 97% RH at 40 degrees C was more profound than 97% RH at 25 degrees C, but both conditions caused a decrease in dissolution, the extent of which was dependent on tablet position in the bottle. Stressed CBZ tablets, however, showed no change in the chemical stability of CBZ under all tested conditions.

Anticonvulsants↗

Stability of freeze-dried tablets at different relative humidities.

The purpose of the study was to evaluate the stability of two different freeze-dried tablet formulations at different relative humidities (RHs). The tablets contained 25 mg hydrochlorothiazide (HCT) as a model drug and were prepared by freeze-drying a suspension and an oil-in-water (o/w) emulsion. Formulation A was a rapidly disintegrating tablet and consisted of 80 mg of maltodextrine DE38; 8 mg of polyethyleneglycol (PEG 6000), 8 mg of xanthan gum, and 25 mg of HCT. Formulation B was a lyophilized dry emulsion tablet that consisted of 160 mg of Miglyol 812, 80 mg of maltodextrin DE38, 16 mg of methylcellulose (Methocel) A15LV, and 25 mg of HCT. Tablets were packaged in different packing materials: polyvinylchloride (PVC)/aluminum blister packs, PVC-polyvinylidenechloride (PVDC)/aluminum blister packs, closed containers with a dessicant tablet, and open containers. The tablets were stored at three relative humidities (45%, 60%, and 85% RH) and were characterized on mechanical strength, residual moisture, porosity, content uniformity, and scanning electron microscopy (SEM) during a period of 6 months. After 1 month at 60% and 85% RH, a strong increase in moisture content (from 2.7% to 6.8%) was seen for the tablets packed in the open and closed containers and for the PVC/aluminum blistered tablets. This increase was higher for formulation A compared to formulation B since B contained 160 mg of triglycerides and was more hydrophobic. This increase in water content was correlated with a decrease in mechanical strength. The tablets also showed a change in microstructure and porosity. At a moisture content of 7.2%, formulation A showed a structural "collapse" since water acts as a plasticizer for the amorphous glass, lowering the glass transition temperature Tg. This phenomenon even occurred in PVC/aluminum blister packs at 85% RH. The structural collapse was associated with a complete loss of microstructure as detected by porosimetric analysis and SEM. For the PVC-PVDC/aluminum blistered tablets, the increase in moisture content and decrease in mechanical strength at 85% RH occurred much slower, and the water uptake and strength loss were less intensive. No significant breakdown of HCT could be observed in both formulations with all of the packing materials. Packaging of freeze-dried tablets with PVC/aluminum blister packs, PVC/PVDC/aluminum blister packs, or closed containers did not offer protection against moisture uptake, mechanical strength loss, and structural collapse.

Aluminum↗

Investigating the fundamental effects of binders on pharmaceutical tablet performance.

For solid dosage forms, a better understanding of the fundamental properties of the binders helps in developing better formulations and products. The objective of this study was to determine the effects of binder toughness and plastic flow on tablet hardness, friability, and capping. The characteristic of binder toughness was determined, and the correlation between the ejection force of the tablet and the toughness of the binder was established. Evaluation was conducted using acetaminophen tablets with different kinds of binders (i.e., hydroxypropylcellulose, methylcellulose [MC], povidone [PVP], starch, etc.). A rotary tablet press was used for tableting at three different speeds. The properties of binders and acetaminophen tablets were determined using a diametral compression test. The toughness was measured as the curve of the area under the load versus deflection. The microbehavior of these binders was also studied. The acetaminophen tablets with the binders were subjected to predetermined loads and then examined under a scanning electron microscope. The tablets that contained hydroxypropylcellulose as a binder showed the highest toughness and had the lowest ejection force. The ejection force of tablets decreased with increasing concentrations of hydroxypropylcellulose in the dosage forms. The tablets that contained other binders failed by capping and random cracking in the middle. These results show that hydroxypropylcellulose, a thermoplastic polymer, provides the best physical characteristics for the tablets. This effect could help in improving tablet manufacturing conditions (e.g., compression force and speed).

Acetaminophen↗

Excipient-excipient interaction in the design of sustained-release theophylline tablets: in vitro and in vivo evaluation.

Sustained-release (SR) theophylline (TPH) tablets were prepared by applying the moisture-activated dry granulation method. The interaction between the excipients sodium alginate (SAL) and calcium gluconate (CG) was the base for the formation of a cross-linked matrix that may regulate TPH release from the formulated tablets. The prepared granules showed good physical characteristics concerning the flow properties and compressibility, with the angles of repose in the range 29-31, and the compressibility indices ranged between 15% and 25%. The granules had low friability values (3.0%-4.2%), depending on SAL:CG ratios. The corresponding tablets showed good physical properties, with a lower rate of drug release compared with the commercial TPH tablets (Quibron). The release of TPH from the prepared tablets was not markedly affected by either the concentration of added dry binder (carbopol 934) or the tablet hardness, indicating that the rate-determining step in drug release was the diffusion through the produced calcium alginate matrix. Tablets formulated with equal ratios of CG and SAL that showed good physical properties and slow TPH release were chosen for bioavailability studies in beagle dogs, and results were compared with those for Quibron. The in vivo data showed a comparable plasma concentration profile for both tablet formulations, with prolonged appearance of drug in the plasma in detectable amounts for up to 24 h. The formulated tablets showed 104.65% bioavailability relative to that of the commercial tablets. The rate and extent of absorption of TPH showed no significant differences from that of the commercial tablets. Moreover, no significant differences were found in the pharmacokinetic parameters related to the rate and extent of TPH absorption from the prepared and commercial tablets.

Alginates↗

Blinding controlled-release tablets for clinical trials.

The objective of the current study was to develop a method to blind commercially available Wellbutrin SR 150 mg sustained-release tablets for a clinical study. Overcoating was selected as the most appropriate blinding method. Hydroxypropyl methylcellulose (Opadry II) containing red iron oxide and titanium dioxide was applied to the Wellbutrin tablets at coating levels ranging from 0.5% to 4% weight gain. When compared against the uncoated product, no significant differences in drug release were noted over an 8-hr period. Matching placebo tablets, prepared using specially designed tablet tooling, were coated with the same cellulosic polymer that was used for the active. The coated active and placebo tablets were virtually indistinguishable. To test the applicability of this overcoating technique for blinding other controlled release products, the same procedure was used to coat Glucotrol XL 5 mg tablets and Theo-Dur 200 mg tablets. The debossing on the Theo-Dur tablets and the laser-drilled hole on the surface of the Glucotrol tablets prevented blinding. The Theo-Dur tablets were mechanically weak and not able to withstand the coating process. Dissolution testing revealed significantly higher amounts of drug were released from the blinded Glucotrol tablets compared to the unblinded product at the 12 hr time point. The findings from this study suggest that overcoating with pigmented hydroxypropyl methylcellulose may not be useful for blinding all controlled-release tablets.

Administration, Oral↗

Safety and colon-cleansing efficacy of a new residue-free formulation of sodium phosphate tablets.

OBJECTIVE: A residue-free sodium phosphate tablet (RF-NaP) was formulated that lacks microcrystalline cellulose, which can appear as a whitish residue in the colon. A multicenter, randomized, investigator-blinded study was conducted to compare the colon-cleansing efficacy of 40 or 32 tablets of RF-NaP with the marketed 40-tablet NaP treatment regimen. METHODS: Eight hundred sixteen patients were randomized prior to colonoscopy to receive either 40 tablets (60 g) of NaP or RF-NaP or 32 tablets (48 g) of RF-NaP. Colon cleansing was assessed using a 4-point scale based on retained "colonic contents." The primary end point was overall colon-cleansing response rate to treatment (score of excellent/good) versus nonresponse (fair/inadequate). RESULTS: Seven hundred four patients were included in the efficacy analysis. The overall colon-cleansing response rates were comparable among treatment arms (94.5%, 97.0%, and 95.3% for NaP, RF-NaP 40, and RF-NaP 32 tablets, respectively). Ascending colon-cleansing response rates for RF-NaP 40 (95.7%) and 32 tablets (93.6%) were significantly better than for NaP tablets (88.5%, p < 0.03 for both). Patients treated with RF-NaP 32 tablets experienced less pronounced changes in electrolyte levels and fewer adverse events (138/239, 58%) compared with patients receiving NaP (161/238, 68%, p= 0.07) and RF-NaP 40 tablets (156/236, 66%, p= 0.03). The most common adverse events reported were abdominal distention, nausea, abdominal pain, and vomiting. CONCLUSIONS: Based on the safety, efficacy, and patient preferences, the 32-tablet RF-NaP regimen was superior to the 40-tablet RF-NaP and NaP regimen for colon cleansing prior to colonoscopy.

Adolescent↗

The practice of splitting tablets: cost and therapeutic aspects.

BACKGROUND: Tablet splitting is used in pharmacy practice to adjust the dose to be administered. It is also being advocated as a method of reducing prescription drug costs. METHODS: The potential for using this practice as a cost-saving method was examined. The top 200 prescription products in Canada were evaluated for their potential for tablet splitting to reduce costs. The assessment was based on the dosage form (only tablets could be split), availability of dosages in multiples, whether the drug was used for long-term therapy, whether the product was packaged suitably (e.g. oral contraceptives in a therapeutic package), whether pricing structure would allow substantial saving, and the physical nature of the tablets (e.g. whether there were special dose-release characteristics). The products most commonly split in three Canadian pharmacies were compared with the products that had a substantial savings potential. Costs for splitting tablets in the pharmacy and costs of instructing patients to split tablets were calculated. RESULTS: Savings could be generated from tablet splitting for only 15 of the 200 products. There was little overlap between these 15 products and the products that were most frequently split in the three pharmacies. The costs associated with tablet splitting in the pharmacy were approximately 0.1 Canadian dollars ($Can) per tablet. The cost of instructing a patient to split the tablets was approximately $Can1. CONCLUSIONS: Tablet splitting appears to have limited usefulness as a cost-reduction strategy. Only a small proportion of products are suitable for splitting and have the potential for savings. There are also costs arising from splitting tablets in the pharmacy, or instructing patients to do so, and from wastage of product. There are also issues such as patient compliance and the risk of an incorrect dose being taken that should be considered.

Cost Savings↗

Influence of plasticizers on tableting properties of polymers.

This study relates tablet formation with relaxation properties of two polymers on the basis of the stress-deformation curve. The mechanical properties of the polymers were varied by changing tableting temperature, adding varying amounts of plasticizer, and incorporating a monomer with plasticizer effect on the polymer chain. The crucial parameter appeared to be the difference between the glass transition temperature and the tableting temperature. This temperature difference was found to determine the amount of energy stored during densification. The energy is manifested as the stress relaxation propensity of the material. Large stress relaxation yields porous and consequently weak tablets. At a low temperature difference (i.e., tableting temperature is much lower than the glass transition temperature), the amount of stored energy is large. An increase in tableting temperature, or a decrease in glass transition temperature, yields a decrease in stored energy as a result of a decrease in yield strength. Consequently, production of less porous and stronger tablet is possible. However, if the tableting temperature is higher than the glass transition temperature, the stress relaxation propensity of the deformed polymers is extremely high because the elastic modulus of the materials is low under these circumstances. This results is porous and even capped tablets. From the data it is concluded that, independent of the type of polymer and the method of plasticizing, compaction at a temperature of about 20 K under the glass transition temperature yields circumstances for which the amount of stored energy has a minimum. Consequently, tablet porosity has a minimum and tablet strength has a maximum. These circumstances are created by changing both the tableting temperature and the glass transition temperature of the powder.

Algorithms↗

[Nausea disintegrating buccal tablet in the prevention of gastrointestinal reaction induced by anticancer drugs].

OBJECTIVE: To evaluate the efficacy and safety of nausea oral, disintegrating buccal tablet (DBT) in the prevention of gastrointestinal reaction induced by anticancer drugs (cisplatin DDP 30 - 50 mg/m(2) or adramycin ADM >/= 40 mg/m(2)), as compared with those of kytril tablets. METHODS: A multicenter, open and randomized self-crossover control trial was carried out with all the eligible patients randomized into AB or BA group. Patients in AB group were given nausea 0.1 mg as buccal tablet one hour before chemotherapy in the first cycle and kytril tablet 2 mg in the second cycle, those in BA group were given these drugs in the reverse order. RESULTS: Seventy-three patients were allotted to this study, including 44 patients in DDP-arm and 29 in ADM-arm. Sixty-two patients were evaluable for response and 70 patients for safety. Nausea DBT was as effective as kytril tablet in the control of anorexia, nausea and vomiting during the first 24 hours after chemotherapy, with response rates of 74.2%, 77.4%, 83.9% in nausea DBT and 74.2%, 71.0%, 88.7% DBT in kytril tablets. A high efficacy in the control of vommitting induced by cisplatin was observed in both nausea DBT and kytril tablets. The complete control rates and overall control rates were 83.3%, 91.7% in nausea DBT and 86.1%, 97.2% in kytril tablets, respectively. The side effects of nausea DBT were head heaviness, dry mouth and somnolence, which were mild and comparable with kytril in their frequencies. CONCLUSION: Nausea disintegrating buccal tablet is able to effectively prevent gastrointestinal reaction induced by anticancer drugs, with efficacy and side effects similar to kytril tablets. Nausea DB tablet, an intraoral disintegrator, is very convenient for patients who can not swallow tablets for various reasons.

Adolescent↗

Comparative human study of ibuprofen enantiomer plasma concentrations produced by two commercially available ibuprofen tablets.

Twelve healthy male subjects participated in a two-way Latin square crossover study in which the treatments were a single 400 mg generic ibuprofen tablet (Tablet A) or a single 400 mg MOTRIN Tablet (Tablet B). Blood samples were drawn at various times through 12 h after dosing and plasma samples were assayed for ibuprofen enantiomers with a stereospecific capillary gas chromatographic procedure. Concentration-time data for both enantiomers were in agreement and indicated that drug was absorbed much more quickly from Tablet B than from the Tablet A; enantiomer Tmax values were less than 1.3 h from Tablet B but longer than 4 h from the Tablet A (p less than 0.001). Also, maximum enantiomer plasma concentrations from the Tablet B were about 50 per cent of the peak concentrations observed from Tablet A (p less than 0.001). The total extent of drug absorption appeared to be the same in both products. These data clearly indicate that the two tablets are not bioequivalent with respect to either ibuprofen enantiomer.

Adult↗

Chlorothiazide absorption from solution and tablet dosage forms in dogs.

The bioavailability of an aqueous solution of chlorothiazide and three commercially available chlorothiazide tablets was assessed in adult mongrel dogs. In two crossover urinary excretion studies, six fasting dogs received single 500-mg doses of chlorothiazide as an aqueous solution, one 500-mg originator tablet on two separate occasions (Tablets A-1 and A-2), two 250-mg originator tablets (Tablet B), or one 500-mg generic tablet (Tablet C). 6-Amino-4-chlorobenzene-1,3-disulfonamide )chloraminophenamide), a pharmacologically active hydrolysis product of chlorothiazide was not detected in any urine sample. Urinary recoveries of chlorothiazide after oral administration, expressed as the mean (range) percent of the dose, was only 22.0 (8.41-33.9), 15.7 (10.2-25.0), 20.7 (7.25-31.0), 18.5 (8.72-33.2), and 21.9% (6.69-41.1%) for the aqueous solution and Tablets A-1, A-2, B, and C, respectively. Considerable interindividual variation and some intraindividual variation were observed. No statistically significant difference in bioavailability existed among the aqueous solution and Tablets A-2 and B, between Tablets A-1 and C, and between Tablets A-1 and A-2.

Animals↗

Development and evaluation of enteric-coated penicillamine tablets.

Commercially available 250-mg penicillamine tablets were converted into enteric-coated tablets. Based on in vitro dissolution and disintegration tests, tablets coated with five layers of a cellulose acetate phthalate formulation by a modified pan coating technique were judged to be superior to other coated tablets. These tablets resisted disintegration in simulated gastric fluid over a 4-h period and disintegrated in an average of 21 min in simulated intestinal fluid. Enteric-coated penicillamine tablets were tested in vivo in nine weanling pigs divided into three groups: a negative control group, a test group dosed with enteric-coated penicillamine tablets, and a positive control group dosed with uncoated tablets. The incidence of GI tract bleeding, as determined by daily occult blood tests of the stools, was significantly less in the animals receiving the enteric-coated tablets when compared with the positive control group. The enteric-coated dosage form appeared to decrease GI tract irritation caused by penicillamine. Plasma concentration-time curves for penicillamine in the pigs were similar in shape to those reported in humans. Atypical double peaks occur in both species. Relative bioavailability of the enteric-coated tablet was found to be 67% when compared with the uncoated tablet. This apparent reduction is probably due to a large intrasubject variation in areas under the plasma concentration-time curves and not to a dosage form effect.

Animals↗

Depth profiling of compression-induced disorders and polymorphic transition on tablet surfaces with grazing incidence X-ray diffraction.

PURPOSE: The importance of induced crystal disorders like crystallite size, crystal defects, and amorphicity with respect to the dissolution rate of the drug has been discussed in many cases. Thus, the characterization of these properties is of great importance in the pharmaceutical formulation development, although the exact correlation between disorders and dissolution rate is still unclear. The aim of this study was to analyze pharmaceutical tablets with grazing incidence X-ray diffraction, which enables the depth profiling of the crystallographic properties of the tablets. To study and clarify the potential of grazing incidence diffraction in the analysis of pharmaceutical materials, the effect of the compaction process on the surface of tablets was examined. METHODS: Carbamazepine, tolbutamide, and chlorpropamide tablets, compacted using different compression pressures, were studied using grazing incidence angle X-ray diffraction. The effects of compression on the crystallographic properties were investigated as a function of the distance from the tablet surface. RESULTS: The surfaces of the tolbutamide and chlorpropamide tablets were disordered due to the compression. The manifestation of the disorder was deduced to be due to amorphicity, small crystallite size, and amount of crystal defects. The changes were mainly on the surface and diminished strongly as a function of the distance from the surface of the tablet. Moreover, the changes were dependent on the compression pressure used. The changes on the surface of the carbamazepine tablets were also due to the compression but these changes were not clearly dependent on the depth nor the compression pressure. The partial phase transition took place in the chlorpropamide tablets due to the compression. The magnitude of the transition was not highest on the surface because amorphization and texturization also took place on the tablet surface during the compression. CONCLUSIONS: The present study proved that grazing incidence X-ray diffraction is a potential novel research tool to reveal crystallographic transformations taking place on the surfaces of the tablets induced, for example, by compression pressure.

Carbamazepine↗

The rationale of scored tablets as dosage form.

The aim of the study was to get insight into the rationale of scored tablets. This was pursued by studying patient's reasons for subdividing ("breaking") scored and unscored tablets. Patients who picked up their prescriptions in 5 community pharmacies in The Netherlands were questioned. Two-hundred and seventy-five prescriptions were studied. Of all dispensed tablets, 31% were subdivided, mostly because a dose that needed subdivision was prescribed. However, 30% were subdivided upon the initiative of the patient himself: 13% for ease of swallowing and 17% because the patient chose to take a lower dose. Even unscored tablets were subdivided: because the dose prescribed was half the tablet dose (6%), for ease of swallowing (1%) and the wish of the patient to take a lower dose (3%). It was also inquired about the patient's perception of the ease of subdivision of scored tablets. Problematic subdivision of scored tablets was reported in 55% of the cases, 42% of which was attributed to a disfunctioning score line. We also studied the possibility to prescribe and dispense other medicinal products as alternatives for tablets that needed to be subdivided. For 46% a dosage form with a lower dose was on the market, for 54% it was not. We conclude that scored tablets still fulfil an important role. Even when lower dosed tablets would become available, there remains a substantial wish of patients to subdivide tablets for ease of swallowing and adapting the dose. Improving the functioning of score lines may be a more practical approach than banning this dosage form.

Administration, Oral↗

Pluronic-g-poly(acrylic acid) copolymers as novel excipients for site specific, sustained release tablets.

Potential utility of copolymers comprising Pluronic (PEO-PPO-PEO) surfactants covalently conjugated with poly(acrylic acid) (PAA) as excipients for sustained-release tablets was explored. Apparent particle density, particle size distribution, Carr index, thermal stability, and compression behavior of the Pluronic-PAA copolymers were characterized. Tablets prepared by direct compression of blends of Pluronic-PAA copolymers were evaluated on the basis of their thermomechanical profile, crushing strength, friability, and drug release properties. Small molecular weight drugs of aqueous solubility decreasing in the order theophylline>hydrochlorothiazide>nitrofurantoin were incorporated to the tablets. For comparison purposes, tablets were also prepared from PAA of Carbopol 71G (C71G), and mixtures of C71G and Pluronic F127, with each of the above three drugs. The Pluronic-PAA aggregates are stabilized by hydrophobic associations between poly(propylene oxide) (PPO) segments in aqueous solutions, and thus require higher ionization of the carboxylic groups to overcome the associations and swell. The swelling pattern of the Pluronic-PAA copolymers is more dramatically pH-dependent than that of Carbopol lacking any hydrophobic associations. The drug retention in and release from the Pluronic-PAA based tablets is profoundly pH-dependent and hence specific to the pH exceeding that of the pK(a)>5 of these copolymers. Theophylline- and hydrochlorotiazide-containing tablets made with Pluronic-PAA copolymers showed a reduced release rate under acidic conditions compared to the neutral or alkaline conditions, while the opposite pattern was observed with the Carbopol-based tablets due to the different pH-dependent swelling behavior of the polymers. Nitrofurantoin-containing tablets showed a remarkably low drug release rate owing to the strong hydrophobic character of nitrofurantoin and of its complexes with the copolymers. Integrity of the nitrofurantoin-containing tablets was maintained during the 24h release test. Zero-order kinetics of the cumulative release profile of all drugs under study was observed with the Pluronic-PAA as a tablet excipient. Adequate mechanical properties, the self-assembling behavior, and the pH-sensitiveness of the Pluronic-PAA copolymers make them promising excipients for tablets with preferential delivery into a neutral to alkaline pH environment.

Acrylic Resins↗

Cyclodextrin-containing poly(ethyleneoxide) tablets for the delivery of poorly soluble drugs: potential as buccal delivery system.

The aim of this work was to develop a tablet for the buccal delivery of the poorly soluble drug carvedilol (CAR), based on poly(ethyleneoxide) (PEO) as bioadhesive sustained-release platform and hydroxypropyl-beta-cyclodextrin (HPbetaCD) as modulator of drug release. As first, PEO tablets loaded with CAR/HPbetaCD binary systems with different dissolution properties were tested for CAR and HPbetaCD release features and compared to PEO tablets containing only CAR. When the drug was incorporated as CAR/HPbetaCD freeze-dried product, all CAR content was released from the tablet in about 10 h, displaying a constant release regimen after a transient. The effect of HPbetaCD incorporation on the release mechanism, was rationalized on the basis of the interplay of different physical phenomena: erosion and swelling of the tablet, drug dissolution, drug counter-diffusion and complex formation. In the second part of the study, the potential of HPbetaCD-containing PEO tablets as buccal delivery system for CAR was tested. It was found that the incorporation of HPbetaCD in the tablet did not alter significantly its good adhesion properties. The feasibility of buccal administration of CAR was assessed by permeation experiments on pig excised mucosa. The amount of CAR permeated from PEO tablet was higher in the case of HPbetaCD-containing tablets, the maximum value being obtained for CAR/HPbetaCD freeze-dried system. Our results demonstrate that, when the tablet is employed as transmucosal system, the role of drug dissolution enhancement in the hydrated tablet is much more relevant than in solution for increasing the delivery rate.

2-Hydroxypropyl-beta-cyclodextrin↗