Plain Tablets Research Articles

Enhancement of dissolution rate and formulation development of irbesartan tablets by employing starch phosphate: A new modified starch

The objective of the present study is to prepare, characterize, and evaluate starch phosphate as a carrier in solid dispersions for enhancing the dissolution rate of irbesartan (IRB). The feasibility of formulating solid dispersions of IRB in starch phosphate into compressed tablets with enhanced dissolution rate was also investigated. Starch phosphate prepared by reacting starch with di‑sodium hydrogen orthophosphate anhydrous at elevated temperatures was insoluble in water and has good swelling (400%) property without pasting or gelling when heated in water. Solid dispersions of IRB in starch phosphate prepared by solvent evaporation method employing various weight ratios of drug: Starch phosphate gave rapid and higher dissolution of IRB when compared to pure drug. The 19.92‑ and 39.98‑fold increase in the dissolution rate (K1) of IRB was observed with solid dispersions ISD4 and ISD5, respectively. The dissolution efficiency up to 30 min (DE30) was also increased from 10.58% in the case of IRB pure drug to 81.77% and 88.28% in the case of ISD4 and ISD5, respectively. IRB tablets formulated employing its solid dispersions in starch phosphate also gave rapid and higher dissolution rate and DE30 when compared to plain and commercial tablets. The 33.82‑ and 59.66‑fold increase in the dissolution rate (K1) was observed with formulations IBTF2 and IBTF3 when compared to formulation IBTF1. Starch phosphate could be used as a carrier to enhance the dissolution rate of IRB from its solid dispersions as well as tablet formulations. Key words: Irbesartan, solid dispersions, starch phosphate, tablets and modified starches

Formulation and Evaluation of Sustained Release Mucoadhesive Atenolol Tablets for Gastric Retention

An oral sustained release gastroretentive dosage form comes out as better alternative for drugs having narrow absorption window. Atenolol conventional tablets have been reported by many scientists to exhibit poor oral bioavailability and fluctuations in plasma drug concentration. This results, either in precipitation of side effects or reduction in drug concentration at the target site. Thus objective of present study was to develop, optimize and evaluate a gastroretentive, mucoadhesive tablet for sustained release. A 22 factorial design was employed to systematically study the drug release profile and bioadhesive strength. Sodium carboxymethyl cellulose (CMC) and carbopol 934P were selected as independent variables. Tablets were prepared by direct compression and were evaluated for tablets characteristics, swelling study, adhesion strength and percent drug released. Optimized formulation was compared with marketed formulation (ATEN-50). In vitro wash off test was applied to study the gastroretentive behavior.Tablets prepared show good tablet characteristics, optimum swelling behavior and high adhesion strength. The optimized batch follows zero order drug release profile with non fickian transport mechanism. The mucoadhesion time for optimised batch (M4) was found to be more than four hours and compared with plain tablet which was found to be very less (less than half hour).Thus, the gastroretension by mucoadhesion proven to be a potential tool for drug atenolol which improves its bioavailability with reduction in dosing frequency and dose related side effects.

Imperatorin sustained-release tablets: In Vitro and pharmacokinetic studies

We prepared and evaluated imperatorin (IMP) sustained-release tablets. IMP is an active compound in Angelica dahuricae, a Chinese herbal medicine. We used different polymers, such as hydroxypropyl methylcellulose (HPMC K4M, K15M, and K100M), carbopol 934P, sodium carboxymethyl cellulose (CMC-Na), and their combinations to prepare the matrix tablets and achieve the desired sustained release profile. The in vitro release profiles of these formulations were examined and fit to various kinetic release models. We also tested the effects of polymer combination ratios on the in vitro release rate. In vivo studies were performed for the optimized formulation in six beagle dogs, and pharmacokinetic parameters were compared with plain IMP tablets. IMP sustained-release tablets exhibited a more sustained plasma concentration than the plain tablets, with a relative bioavailability of 127.25%. The in vitro releases rates and in vivo absorption correlated for the initial 8 hours. These results demonstrate that the sustained-release tablet system can effectively control the release of IMP.

Formulation Studies on Solid Dispersions of Mefenamic Acid in Superdisintegrants

The feasibility of formulating the solid dispersions of mefenamic acid into tablet dosage forms is evaluated. All the tablets formulated employing solid dispersions of mefenamic acid in superdisintegrants gave rapid and higher dissolution of mefenamic acid when compared to that of mefenamic acid plain tablets. The increasing order of dissolution rate of formulated tablets with various carriers was Croscarmellose (CC)>Pregelatinised starch (PGS) > Primojel(PJ) > Crospovidone (CP). The same order of performance was observed with tablets formulated employing superdisintegrants alone and in combination with PVP.A 2.75 fold increase in the dissolution rate of mefenamic acid was observed with tablets formulated employing its solid dispersions in CC (MAF4) when compared to plain tablets (MAF1). A 6.97 fold increase in the dissolution rate of mefenamic acid was observed with tablets formulated employing its solid dispersions in combined carriers CC and PVP (MAF8) when compared to its plain tablets (MAF1).

Characterization of ternary complexes of meloxicam-HPβCD and PVP or L-arginine prepared by the spray-drying technique

Ternary complexes of meloxicam (ME) (a poorly water soluble anti-inflammatory drug) with hydroxypropyl-beta-cyclodextrin (HPbetaCD) and either a hydrophilic polymer, namely, polyvinyl pyrrolidone (PVP) or a basic amino acid such as L-arginine, were prepared by the spray-drying technique. The solubilizing efficiency, physical properties and dissolution behaviour of each ternary system of ME-HPbetaCD with either PVP or L-arginine were compared with those of the corresponding binary system of ME-HPbetaCD. Tablets compressed from the ternary system of ME-HPbetaCD-L-arginine were compared with plain and commercial tablets. Phase solubility experiments suggested the formation of an inclusion complex of AL type. Ternary system of ME-HPbetaCD-L-arginine exhibited a stability constant 30.3 times higher than the binary system of ME-HPbetaCD, while the ternary system of ME-HPbetaCD-PVP increased the stability constant 2.2 times only. The prepared complexes were characterized by scanning electron microscopy, differential scanning calorimetry and infra red spectroscopy. Ternary solid complexes indicated the presence of strong interactions between the components. The dissolution behaviour of ME from different ternary complexes was higher than its dissolution from the binary system. Tablets compressed from ternary complexes of ME-HPbetaCD-L-arginine highly improved drug release compared to plain and commercial tablets.

Solubility enhancement and development of dispersible tablet of meloxicam

The present research work investigates enhancement of dissolution profile of meloxicam using solid dispersion (SD) with various polymers. The work also describes the formulation of dispersible tablet (DT) and effervescent tablet of meloxicam. PEG 6000, PEG 8000, PEG 20000, Lutrol F-127, and β-cyclodextrin were selected for the preparation of SD. The SDs were prepared by melting and solvent evaporation methods. Dissolution studies were performed for plain meloxicam, SDs, and tablet formulations. Infrared spectroscopy and differential scanning calorimetry were performed to identify the physicochemical interaction between drug and carriers. Dispersible tablets and effervescent tablets were compared with tablet containing plane drug for dissolution profile. Dissolution of DT improved significantly in SD product (<95% in 1 min).

In vitro and in vivo evaluation of tegaserod maleate pH-dependent tablets

The purpose of this study was to prepare tegaserod maleate (TM) pH-dependent tablets and evaluate their advantages as a sustained release delivery system. TM, insoluble in water and unstable in gastric milieu, was formulated into pH-dependent tablets coated with combinations of two methacrylic acid copolymers - Eudragit L100 and Eudragit S100. The influence of core tablet compositions, polymer combination ratios and coating levels on the in vitro release rate of TM from coated tablets was investigated. The optimum formulation was evaluated for in vitro release rate and in vivo bioavailability study on beagle dogs. In addition, physico-chemical properties of the drug, including solubility at different pH and temperatures, and dissociation constant were determined. The results showed that no drug was released in 0.1 mol/L hydrochloric acid within 2h, and about 90% of the drug was released in the pH 6.8 phosphate buffer within 12h in a sustained manner. The pharmacokinetic investigation showed that TM pH-dependent tablets exhibited a sustained plasma concentration, a lag time of approximately 2.3h and a relative bioavailability of 159% compared to plain tablets. A close correlation existed between the in vitro release rate of the pH-dependent system and its in vivo absorption percentage. The results of the present study have demonstrated that the pH-dependent tablet system is a promising vehicle for preventing rapid hydrolysis in gastric milieu and improving oral bioavailability of TM for the treatment of irritable bowel syndrome.

Different Roles of Pummelo Furanocoumarin and Cytochrome P450 3A5*3 Polymorphism in the Fate and Action of Felodipine

Herein we aim to test if pummelo furanocoumarins can inhibit cytochrome P450 (CYP) 3A both in vitro and in vivo, and to explore the influence of CYP3A5*3 (GenBank AC005020: A22893-->G) polymorphism in the pharmacokinetics and pharmacological response to felodipine. Fruit juices of pummelo grapefruit (Citrus paradisi Macf., G), 'Guanximiyou' (C. grandis Osbeck vs. Guanxi, P) and 'Changshanhuyou' (C. changshanhuyou Y.B. Chang, H) were selected by screening Citrus fruit juices for their furanocoumarin contents and their inhibition of testosterone 6beta-hydroxylation in human liver microsomes. Twelve healthy male Chinese were administered 250 mL G, P, H or water (W) alternatively with 26-mumol (10-mg) plain tablet felodipine, and were observed for 12 h. G had more furanocoumarins and at higher levels than P while H had none, and their potencies for in vitro CYP3A inhibition were in the order as G > P > H. The geometric mean and 90% confidence intervals of pharmacokinetic parameters for human oral felodipine with G, P, H and W were respectively as follows: peak plasma concentration (nmol.L(-1)), 37 (32-44), 25 (21-29), 19 (16-22) and 18 (15-21); area under the plasma concentration-time curve (nmol.h.L(-1)), 118 (103-136), 84 (73-97), 64 (56-74) and 59 (51-68). Subjects showed higher heart rates with G than with H or W. CYP3A5*3 polymorphism showed no significant effect on felodipine pharmacokinetics and related hemodynamic changes. This work supports the hypothesis that CYP3A inhibition by furanocoumarins caused pummelo fruit juice-drug interaction; while the role of CYP3A5 in the population pharmacokinetics of felodipine and blood pressure response appear to be limited.

Evaluation of acrylamide-grafted-xanthan gum copolymer matrix tablets for oral controlled delivery of antihypertensive drugs

The present study was conducted to investigate the utilization of xanthan-grafted copolymer of acrylamide (AAm) as a controlled release (CR) matrix for antihypertensive drugs such as atenolol (ATL) and carvedilol (CDL). Graft copolymerization of AAm onto xanthan gum (XG) was carried out by taking two different ratios of XG to AAm (1:5, 1:10) by free radical initiation polymerization using ceric ammonium nitrate (CAN). Tablets were prepared from plain XG, its grafted copolymer with AAm, and other excipients by incorporating ATL and CDL, which have different physicochemical properties. In vitro release studies were performed in simulated gastric fluid (SGF) followed by simulated intestinal fluid (SIF) without enzymes at 37 °C. Effect of grafting ratio, drug loading, and other excipients on the release kinetics were evaluated for both the class of drugs. The release time increased with increasing grafting ratio and swelling was carried out in SIF at 37 °C, which indicated that XG exhibited maximum swelling compared to graft copolymers. The surface morphology of plain XG, modified XG, and tablet surfaces was studied by scanning electron microscopy (SEM), which revealed that grafting introduced major changes on surface morphology as well as size of the particles. The nature of drug transport through matrix tablets followed the non-Fickian (anomalous) trend. Statistical analyses of release data were performed using analysis of variance (ANOVA) method, which indicated a significant difference in the release rate of ATL from the tablets prepared from XG and the grafted copolymer. The in vitro release studies were also carried out on commercial tablet formulations of ATL and CDL. The release rate of CDL containing tablets with XG and grafted copolymer did not show significant difference, whereas CDL containing tablets with XG, grafted copolymer, and commercial formulations have shown significant differences. Matrix tablet formulations along with the excipients were characterized by Fourier transform infrared spectrophotometer (FT-IR), which indicated no interaction between drugs and the polymers.

Sustained-release tablets of indomethacin-loaded microcapsules: Preparation, in vitro and in vivo characterization

Indomethacin (IDM) was encapsulated in gelatin-cellulose acetate phthalate (CAP) microcapsules (A) by complex coacervation method and in CAP microcapsules (B) by simple coacervation method. Microcapsules A and B, having mean diameters of 38.24 and 35.74 μm, respectively, were used to prepare sustained-release tablets A and B. The activation energy of thermal degradation for tablets A and B was calculated based on differential scanning calorimetry (DSC) to be 258.9 and 284.8 kcal/mol, respectively. In vitro release profiles showed no burst effect and release t 1/2 of the two sustained-release tablets were found to be 41.30 ± 1.86 and 33.25 ± 2.84 min, respectively, while that of IDM plain tablets C was 6.30 ± 0.39 min ( P < 0.01). In vitro release of IDM from tablets A and B could be described by Higuchi equation and zero-order kinetics, respectively. After per os (po) administration with physiological saline, their irritation to rat stomach was obviously reduced in comparison with tablets C. Pharmacokinetic study in rabbits showed that t max was delayed and C max lowered compared with tablets C and the values of AUC 0–24 h of the three tablets were very close.

Adhesive tablet effective for treating canker sores in humans

A new mucoadhesive tablet, which releases natural active agents for pain reduction and rapid healing of canker sores, has been prepared and characterized. Adhesive tablets were prepared by compression molding of mixed powders of crosslinked polyacrylic acid and hydroxypropyl cellulose, absorbed with citrus oil and magnesium salt. The rate of tablet erosion and the rates of citrus oil and magnesium release were determined as well as the adhesiveness of the tablet using bovine gingival tissue and an Instron tensiometer. A clinical trial was conducted on 248 volunteers who had canker sores. Tablets adhere well to the mucosal tissue and gradually erode for 8 h releasing the citrus oil in a zero‐order pattern whereas the magnesium is released during a period of 2 h. Both experimental and plain tablets were effective in reducing pain and decreasing healing time (p < 0.05) without adverse side effects. However, the tablets loaded with active agents were more effective. © 2004 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:2927–2935, 2004

速崩壊錠に対する軽度えん下障害患者の評価

Rapidly disintegrating tablets (“EMP-tablet”, developed by Eisai, Co., Ltd.) are developed based on a formulation that is expected to make the swallowing of medicines easier for patients with mild dysphagia. To evaluate the sensation of the oral administration of such “EMP-tablets”, the authors conducted a study in patients with mild dysphagia. After the administration of both “EMP-tablets” and uncoated compressed tablets of consisting of the same components and the same appearance (plain tablet), the sensation of their oral administration and other benefits such as size and so on, were compared for both tablets.The 25 subjects with mild dysphagia, who participated in the trial were asked to respond to the question “which tablet was easier to swallow?”. The rate of positive responses for the “EMP-tablet” was 76%, which was significantly better (p=0.0013) than the response for the “plain tablet”. Regarding the question about the size of a tablet, although only 28% responded “It is no problem” before oral administration, the response improved to 80% after oral administration. In addition, there was also a statistically significant difference (p=0.0096) in the ratio of patients who required less water for the oral intake of “EMP-tablets” than “plain tablets” (60% vs 16%).Consequently, in patients with mild dysphagia, the clinical benefits of “EMP-tablets” were clearly observed regarding the level of satisfaction during oral administration (tablet size and so on, as well as the required amount of drinking water) in comparison to “plain tablets”.

A PHARMACOKINETIC COMPARISON OF THE MODIFIED RELEASE CAPSULE AND A PLAIN TABLET FORMULATION OF MEBEVERINE

SUMMARYThis study was conducted to compare the pharmacokinetic properties of the modified release 200 mg capsule of mebeverine and the plain 135 mg tablet of mebeverine after single and multiple doses in 12 healthy subjects in a randomised, crossover design. Single doses were given on days 1 and 7 and multiple doses (200 mg b.i.d. for the capsule and 135 mg t.i.d. for the tablet) on days 2–6 of the study. The 200 mg modified release capsule of mebeverine has extended release Properties, as indicated by a lower Cmax, a later tmax and a longer elimination half‐life than the plain tablet, while the bioavailability is optimal. No significant accumulation occurs after multiple doses of either formulation. The twice‐daily dosage regimen of the 200 mg modified release capsule is a good alternative to the three times daily dosage regimen of the 135 mg plain tablet, because the reduced daily intake is likely to benefit patient compliance.

Potentiometric determination of acetylsalicylic acid by sequential injection analysis (SIA) using a tubular salicylate-selective electrode.

This paper deals with the development of an automated procedure for formulation assays and dissolution tests based on a sequential injection analysis (SIA) system involving an ion-selective electrode as sensing device. Construction of a tubular salicylate (Sal) selective electrode suitable for potentiometric determination of acetylsalicylic acid (Asa) in pharmaceutical formulations is described. The flow-through electrode is formed by a PVC membrane containing 29.2% (w/w) PVC, 5.8% (w/w) tetraoctylammonium salicylate (ionic sensor), 58.5% o-nitrophenyloctylether (plasticizer) and 6.5% (w/w) p-tert-octylphenol (stabilising additive which increases electrode selectivity). The calibration range is 0.05--10 mM Sal, the limit of detection (LOD) is 0.05 mM Sal, the slope is 56.0 mV per decade at 22 degrees C. The R.S.D. is 0.20% (15 readings) when determining 2.5 mM Sal in standard solution. The electrode is used for sensing Asa after its on-line chemical hydrolysis to Sal in a SIA system. The sampling rate is 6 h(-1) but for the dissolution tests the frequency is increased to 20 h(-1). The SIA set-up is employed for the assay of Asa in plain tablets, composed tablets and effervescent tablets and for performing dissolution tests of normal and sustained release tablets. Results obtained by this technique compare well with those required by the US Pharmacopoeia XXIV.

The study of the applicability of content uniformity and weight variation test--the state of commercial tablets and capsules in Japan.

This study intends to determine the rational criteria (e.g., threshold value) for applying the weight variation test and to investigate the adequacy of the acceptance value for existing commercial products in Japan. The studied products were 489 lots (3 lots x 163 products) of compressed tablets (plain, film-coated, sugar-coated) and 42 lots (3 lots x 14 products) of hard capsules marketed in Japan. The individual drug content and the weight of 10 units in a lot were determined for each product and the acceptance values were calculated according to the Japanese Pharmacopoeia thirteenth edition (JP13) Content Uniformity Test (M=100.0, k=2.2). Product-specific intra-lot relative standard deviation of content (RSDD), weight (RSDW) and concentration (RSDC) were calculated by analysis of variance (ANOVA) using three lots of data per product. The RSDD and RSDC tended to increase with the decrease of the label strength for plain tablets, but not for film-coated and sugar-coated tablets, and hard capsules. A good correlation was found between RSDD and RSDC but not between RSDD and RSDW. These findings indicate that 1) it is difficult to rationally set the threshold level for weight variation, especially regarding the dosage forms except for plain tablets, 2) the application of weight variation tests should, in principle, be decided on the mixing homogeneity that is RSDC. 3) Most (99.6%) of the tablets and all the capsules investigated met the requirement of content uniformity test of JP13. Therefore the criteria of the JP13 content uniformity test are considered acceptable from the viewpoint of manufacturing capability.

Laparoscopic donor nephrectomy

(Fig. 2). Intraoperatively, two renal arteries were found originating in close proximity from the aorta (Fig. 2A). Each was taken separately, and a common orifice was reconstructed prior to transplantation in the recipient’s left iliac fossa. Warm ischemic time was 4 minutes and 20 seconds; estimated blood loss was 200 cc. There were no intraoperative complications, and the combined procedure took 4 hours, 24 minutes. The donor was discharged on the second postoperative day. She had required only 38 mg of morphine sulfate during the hospitalization. Upon discharge, only four acetaminophen with codeine tablets and eight plain acetaminophen tablets were required for pain relief. She returned to her usual activities, including child care for her granddaughter, two weeks postoperatively. She has had no long-term complications after six months of follow-up. The allograft functioned immediately upon placement in the CASE PRESENTATION recipient. The recipient was treated with tacrolimus, mycopheA 51-year-old woman presented for evaluation to donate a nolate mofetil, and prednisone, our standard immunosuppreskidney to her daughter-in-law, who had end-stage renal disease sive regimen. By day 4, the serum creatinine had decreased secondary to hypertension. The woman had no significant renal from 9.5 mg/dL to 1.5 mg/dL. The recipient was discharged on or urologic history. However, she had a history of irritable postoperative day 5. She has had no episodes of rejection. Her bowel syndrome, which had been treated with dietary manipucreatinine clearance 8 months postoperatively was 60 mL/min. lation. She had undergone an ovarian resection, appendectomy, and previous left laparoscopic oophorectomy for an ectopic pregnancy. She had no allergies and was not taking any medicaDISCUSSION tions. She did have intermittent symptoms of chronic cystitis. She was a full-time homemaker and was involved in taking Dr. Louis R. Kavoussi (Chief, Department of Urolcare of her 8-month-old granddaughter. ogy, Johns Hopkins Bayview Medical Center, and Patrick Physical examination was unremarkable, as was psychologiC. Walsh Distinguished Professor of Urology, Johns Hopcal screening. Laboratory studies were normal including comkins University, Baltimore, Maryland, USA): Kidney plete blood count, liver function study, and serum electrolytes. transplantation is the best option for treating end-stage Her BUN was 7 mg/dL; serum creatinine, 0.8 mg/dL; and creatinine clearance, 119 mL/min. A hepatitis profile and viral antirenal disease. Unfortunately, a large disparity exists bebody screening were negative. She was ABO compatible with tween the number of individuals who could benefit from her daughter-in-law, and HLA typing demonstrated a twothis treatment and the number of available kidneys. Moreantigen match. over, this disparity has worsened over the past few years, Preoperative three-dimensional computerized tomography as evidenced by increased waiting times for recipients (CT) reconstruction revealed a single renal artery with an early bifurcation as well as normal venous anatomy (Fig. 1). Both [1]. For example, at our institution, the average waiting kidneys appeared equal in size. A large gallstone was noted. time for a cadaveric kidney transplant has increased from Nine months ago, she underwent a left laparoscopic donor two years in 1990 to four years currently. Because the nephrectomy and simultaneous laparoscopic cholecystectomy. supply of cadaveric kidneys has remained relatively The kidney was removed through a Pfannenstiel incision. Two fixed, alternative sources of organs have been sought 1 cm and one 0.5 cm incisions were used for the dissection over the last decade. One great potential means for obtaining more kidneys The Nephrology Forum is funded in part by grants from AstraZeneca is through live donation. When compared with cadaveric LP; Amgen, Incorporated; Merck & Co., Incorporated; Dialysis Clinic, renal transplantation, living-donor transplantation has Incorporated; and R & D Laboratories. several advantages, including greater patient and graft

Stability studies of aspirin–magaldrate double layer tablets

Accelerated stability testing was performed on aspirin–magaldrate double layer tablets as well as aspirin–maalox marketed double layer tablets (Ascriptin®) in order to evaluate the effect of the presence of the alkaline moieties of the antacid (magaldrate and maalox) on the chemical stability of aspirin. The results were compared simultaneously with that obtained from the marketed Aspro® plain tablets. The results revealed that the presence of the alkaline moieties in the tested tablets has increased the rate of aspirin decomposition and reduced its shelf-life. This effect was more pronounced for aspirin tablets containing magaldrate antacid. Determination of shelf-lives at 25°C for the prepared and the marketed tablets was carried out using Arrhenius plots and the results showed that they were 35, 34.5 and 13.5 months for Aspro®, Ascriptin® and aspirin–magaldrate double layer tablets, respectively. The effect of storage for 50 days and at different temperatures, on the crushing strength and the disintegration time of the prepared and the marketed tablets showed a slight decrease in the disintegration time and the crushing strength of the tablets as the storage temperature increased. Aspro® tablets did not produce the same results. The in vitro release data of the prepared aspirin–magaldrate double layer tablets and the marketed Ascriptin® tablets stored for 50 days and at different storage temperatures as well as Aspro® tablets stored at 70°C were best fitted to the first-order kinetics model. The release data of Aspro® tablets stored at 50 and 60°C for 50 days were best fitted to Higuchi's model.

A comparative bioavailability study of different aspirin formulations using on-line multidimensional chromatography

A multi-dimensional column chromatographic method employing UV spectrometric detection was optimised and successfully used in a comparative bio-availability study of aspirin obtained from different commercially available oral dosage forms. Sample clean-up was achieved by on-line solid-phase extraction. In this study, the bioavailability of aspirin was compared in plain aspirin tablets, chewed tablets, effervescent tablets and Enteric-coated aspirin tablets. Blood samples were taken at frequent intervals after single dosing in ten healthy volunteers, the plasma samples were first treated with physostigmine sulphate to minimise enzymatic hydrolysis of aspirin to salicylate. The results showed the measured T max, C max and AUC was significantly higher for soluble aspirin than for the other formulations and the t 1/2 was shorter. This indicates the rapid absorption of aspirin from a soluble formulation compared with that from the other formulations. These differences suggest that the soluble formulation could be the aspirin of choice to treat patients suspected to be at high risk of myocardial infarction. The method performs, in a single step, an efficient extraction and clean-up of aspirin from human plasma. The calibration graph was linear over the calibration range 0.2–12 μg ml −1 plasma with a limit of detection of 0.1 μg ml −1. The intra- and inter-assay coefficients of variation were less than 6% and the recoveries ranged from 86 to 98%. The proposed method combines the advantages of being simple and selective in the presence of other potential interfering drugs and is suitable for routine analyses to obtain valuable information about the clinical effects of the drug and its use in prevention treatments of acute myocardial infarction. The whole procedure takes ∼7 min and is in agreement with other conventional methods.

AAAIn Vitro Release Evaluation of Hydrocortisone Liquisolid Tablets

The potential of liquisolid systems to improve the dissolution properties of water-insoluble agents was investigated using hydrocortisone as the model medication. The in vitro release patterns of this very slightly water-soluble corticosteroid, formulated in directly compressed tablets and liquisolid compacts, were studied at different dissolution conditions. The new formulation technique of liquisolid compacts was used to convert liquid medications such as solutions or suspensions of hydrocortisone in propylene glycol, a nonvolatile liquid vehicle, into acceptably flowing and compressible powders by blending with selective powder excipients. Several liquisolid tablet formulations were prepared using a new mathematical model to calculate the appropriate quantities of powder and liquid ingredients required to produce acceptably flowing and compressible admixtures. Due to their increased wetting properties and surface of drug available for dissolution, liquisolid compacts demonstrated significantly higher drug release rates than those of conventionally made, directly compressed tablets containing micronized hydrocortisone. The in vitro drug dissolution rates of liquisolid tablets were found to be consistent and independent of the volume of dissolution medium used, in contrast to the plain tablets which exhibited declining drug release patterns with decreasing dissolution volumes. it has been also shown that the fraction of molecularly dispersed drug in the liquid medication of liquisolid systems is directly proportional to their hydrocortisone dissolution rates.

Enhancement of prednisolone dissolution properties using liquisolid compacts

The in-vitro release characteristics of prednisolone, a very slightly water soluble glucocorticoid, formulated in directly compressed tablets and liquisolid compacts, were studied at different dissolution conditions. According to the new formulation method of liquisolid compacts, liquid medications such as solutions or suspensions of water insoluble drugs in suitable non-volatile liquid vehicles, can be converted into acceptably flowing and compressible powders by blending with selected powder excipients. It has been speculated that such systems exhibit enhanced release profiles due to the increased wetting properties and surface of drug available for dissolution. In the present study, the potential of liquisolid systems to improve the dissolution properties of water-insoluble agents was investigated using prednisolone as the model drug. Several liquisolid tablet formulations were prepared using a new mathematical model to calculate the appropriate quantities of powder and liquid ingredients required to produce acceptably flowing and compressible admixtures. Liquisolid compacts demonstrated significantly higher drug release rates, in different dissolution media and volumes, compared to tablets prepared by the direct compression method. It was also observed that the drug dissolution rate from liquisolid tablets was independent of the volume of dissolution medium, in contrast to the plain tablets which exhibited declining drug release patterns with decreasing dissolution volumes.