Investigations on Compaction Behavior of Kollidon®SR-Based Multi-component Directly Compressed Tablets for Preparation of Controlled Release Diclofenac Sodium.

The physics of tablets mixtures has gained much attention lately. The purpose of this work is to evaluate the compaction properties of Kollidon® SR (KSR) in the presence of different excipients such as Microcrystalline cellulose (MCC), Monohydrous lactose (MH Lactose), Poly (vinyl acetate) (PVA100), and a water-soluble drug Diclofenac sodium (DNa) to prepare once daily formulation. Tablets were prepared using direct compression and were compressed into flat-faced tablets using hydraulic press at various pressures. The combination of MCC and KSR in the tablets showed reduced porosity, and almost constant low Py values as KSR levels increased; also, KSR-DNa tablets had higher percentage porosity and crushing strength values than KSR-MH Lactose tablets. The crushing strengths of KSR-MCC tablets were larger than those of KSR-DNa tablets. Ternary mixture tablets comprised of KSR-MCC-DNa showed decreased porosities and low Py values as the percentage of KSR increased especially at high compression pressures but had higher crushing strengths compared to KSR-DNa or MCC-DNa binary tablets. KSR-MH Lactose-DNa ternary tablets experienced lower porosities and crushing strengths compared to KSR-MCC-DNa tablets. Quaternary tablets of KSR-PVA100-MCC-DNa showed lower porosity and Py values than quaternary tablets obtained using similar proportion of MH Lactose instead of MCC. In conclusion, optimum quaternary tablets were obtained with optimum crushing strengths, relatively low Py, and moderate percentage porosities among all prepared quaternary tablets. The drug release of the optimum quaternary tablets demonstrated similar in vitro release profile compared to that of the marketed product with a mechanism of release that follows Korsmeyer-Peppas model.

Effect of strength and porosity of tablets on the magnitudes of subdivision forces.

In this study, a hardness tester was modified by attaching a metal blade to its testing area to obtain the minimum forces required to subdivide tablets along their diameters (F'). Moreover, the tensile strengths of subdividing tablets (TS') were calculated. Tablets of microcrystalline cellulose (MCC) weighing 0.5 g were produced at applied compression pressures of 21, 31, 41, 50, and 60 MPa. In addition, tablets of Ludipress®, and a 5:2 mixture of paracetamol to MCC weighing 0.7 g were produced at applied compression pressures of 77, 116, 154, 193, and 232 MPa. It was found that F' increased as the applied compression pressure used to produce the tablets increased until a maximum value was reached. This maximum value was at around 100 N for MCC and Ludipress® tablets and at around 76 N for paracetamol/MCC tablets. Moreover, a maximum value of TS' was reached at a porosity of 0.37 for MCC, 0.15 for Ludipress®, and 0.11 for paracetamol/MCC tablets. The maximum TS' values were at around 1.5 MPa for MCC and Ludipress® tablets and at around 0.9 MPa for paracetamol/MCC tablets. Therefore, both inter particulate bonding (tablet strength) and porosity (packing) affected the magnitudes of F' and TS'.

The Influence of Drugs Solubilities and Chitosan-TPP Formulation Parameters on the Mean Hydrodynamic Diameters and Drugs Entrapment Efficiencies into Chitosan-TPP Nanoparticles.

Chitosan is a natural, biocompatible polymer. The aim of this work was to study the influence of drug solubility in 2% v/v acetic acid, formulation parameters, on mean hydrodynamic (MHD) diameters and drug entrapment efficiencies (% EE) into chitosan-TPP nanoparticles (NPs). Drugs of different aqueous solubilities with nearly similar molecular weights were chosen and admixed at several concentrations in 2% acetic acid at different chitosan concentrations and at fixed chitosan to TPP concentrations/volumes ratios. The NPs were freeze-dried, and the supernatants were utilized to determine % EE. Theophylline- and antipyrine-loaded NPs showed the best short-term physical stability in terms of MHD diameters. Antipyrine-loaded NPs possessed the larger MHD diameters, while vitamin C-loaded NPs showed the smallest ones. The relationships between the ratio of drug concentration relative to their solubilities in acetic acid were almost linear for antipyrine and vitamin C-loaded NPs when plotted against and the MHD diameters of NPs, and linear for antipyrine- and theophylline-loaded NPs when plotted against % EE with antipyrine NPs possessing the highest % EE. However, vitamin C- and propylthiouracil-loaded NPs exhibited curvilinear patterns with comparatively lower % EE. The concentration of chitosan, drug solubility in dispersion medium, and the ratio of the concentration of admixed drug relative to its solubility in dispersion medium were found critical in determining % EE and MHD diameters of NPs. It was evident that drugs with extremely low or high solubilities in dispersion medium resulted in low % EE when admixed at both low and high concentrations.

Preparation and Evaluation of Ternary Polymeric Blends for Controlled Release Matrices Containing Weakly Basic Model Drug.

OBJECTIVE: The objective of this study was to evaluate the suitability of a ternary mixture of smart polymers comprised of Eudragit®E100, Eudragit®L100, and sodium alginate to serve as a carrier for sustained drug release for weakly basic drugs. The model drug chosen in this part of the study is Metronidazole. METHODS: Matrix tablet formulations were prepared by either direct compression or by wet granulation. Dissolution studies were conducted using USP XXΠ rotating paddle apparatus in three different consecutive stages (pH 1.2, 4.8, and 6.8). Tablets made of low to intermediate proportions of sodium alginate and approximately equal proportions of Eudragit®E100 and Eudragit®L100 were found to have a significant modification of drug release rates. RESULTS: Thus, indicating a potential for controlling the drug release for 12 hours depending on polymers ratios in the formulation. The ratio of sodium alginate to total Eudragit® polymers and the ratio of Eudragit®E100 to Eudragit®L100 within the ternary polymeric composition were found critical in determining the controlled release performance. CONCLUSION: Results of swelling studies were in agreement with the dissolution behaviors of the tablets. The findings suggest the significance of the ternary polymeric compositions in controlling the release of a weakly basic drug, Metronidazole.

Effect of different splitting techniques on the characteristics of divided tablets of five commonly split drug products in Jordan

OBJECTIVE: To determine the accuracy, variability, and weight uniformity of tablet subdivision techniques utilized to divide the tablets of five drug products that are commonly prescribed for use as half tablets in Jordan. METHODS: Ten random tablets of five commonly subdivided drug products were weighed and subdivided using three subdivision techniques: hand breaking, kitchen knife, and tablet cutter. The five commonly subdivided drug products (warfarin 5 mg, levothyroxine 50 μg, levothyroxine 100 μg, candesartan 16 mg, and carvedilol 25 mg) were weighed. The weights were analyzed for acceptance, accuracy, and variability. Weight variation acceptance criteria were adopted in this work as a tool to indicate the properness of the subdivision techniques used to produce acceptable half tablets. Other relevant physical characteristics of the five products such as tablet shape, dimensions, face curvature, score depth, and crushing strength were measured. RESULTS: All tablets were round in shape, had weights that ranged between 100.63 mg (standard deviation=0.99) and 379.04 mg (standard deviation=3.00), and had crushing strengths that ranged between 23.29 N (standard deviation=3.58)and 103.35 N (standard deviation=14.98). Both candesartan and carvedilol were bi-convex in shape with an extent of face curvature equal to about 33%. In addition, percentage score depth of the tablets had a range between 0% and 24%. The accuracy and variability of subdivision varied according to the subdivision technique used and tablet characteristics. Accuracy range was between 81% and 109.8%. Moreover, the relative standard deviation was between 1.5% and 17.4%. Warfarin 5 mg subdivided tablets failed the weight variation test regardless of the subdivision technique used. Subdivision by hand produced half tablets that were acceptable for levothyroxine 50 μg and levothyroxine 100 μg. Subdivision by knife produced half tablets that were acceptable only for candesartan tablets. However, the tablet cutter produced half tablets that passed the weight variation test for four out of the five drug products tested in this study. CONCLUSIONS: The tablet cutter performed better than the other subdivision techniques used. It produced half tablets that passed the weight uniformity test for four drug products out of the five

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Effect of different splitting techniques on the characteristics of divided tablets of five commonly split drug products in Jordan.

OBJECTIVE: To determine the accuracy, variability, and weight uniformity of tablet subdivision techniques utilized to divide the tablets of five drug products that are commonly prescribed for use as half tablets in Jordan. METHODS: Ten random tablets of five commonly subdivided drug products were weighed and subdivided using three subdivision techniques: hand breaking, kitchen knife, and tablet cutter. The five commonly subdivided drug products (warfarin 5 mg, levothyroxine 50 µg, levothyroxine 100 µg, candesartan 16 mg, and carvedilol 25 mg) were weighed. The weights were analyzed for acceptance, accuracy, and variability. Weight variation acceptance criteria were adopted in this work as a tool to indicate the properness of the subdivision techniques used to produce acceptable half tablets. Other relevant physical characteristics of the five products such as tablet shape, dimensions, face curvature, score depth, and crushing strength were measured. RESULTS: All tablets were round in shape, had weights that ranged between 100.63 mg (standard deviation=0.99) and 379.04 mg (standard deviation=3.00), and had crushing strengths that ranged between 23.29 N (standard deviation=3.58)and 103.35 N (standard deviation=14.98). Both candesartan and carvedilol were bi-convex in shape with an extent of face curvature equal to about 33%. In addition, percentage score depth of the tablets had a range between 0% and 24%. The accuracy and variability of subdivision varied according to the subdivision technique used and tablet characteristics. Accuracy range was between 81% and 109.8%. Moreover, the relative standard deviation was between 1.5% and 17.4%. Warfarin 5 mg subdivided tablets failed the weight variation test regardless of the subdivision technique used. Subdivision by hand produced half tablets that were acceptable for levothyroxine 50 µg and levothyroxine 100 µg. Subdivision by knife produced half tablets that were acceptable only for candesartan tablets. However, the tablet cutter produced half tablets that passed the weight variation test for four out of the five drug products tested in this study. CONCLUSIONS: The tablet cutter performed better than the other subdivision techniques used. It produced half tablets that passed the weight uniformity test for four drug products out of the five.

Anti-factor Xa levels in obese patients receiving enoxaparin for treatment and prophylaxis indications.

OBJECTIVES: To evaluate the degree of anticoagulation achieved with different enoxaparin dosing regimens used in obese and morbidly obese patients in a hospital setting in Jordan. METHODS: All obese adult patients who were prescribed enoxaparin for various indications were invited to participate in the study. The anti-factor Xa (anti-Xa) level was checked once after 4-6 hours of the third or fourth dose of enoxaparin (at steady state). Patients were followed daily to evaluate drug efficacy and safety through their hospital course. RESULTS: Enoxaparin daily dose used for prophylaxis indications ranged from 0.3 to 0.85 mg/kg and from 0.31 to 2.25 mg/kg in case of certain treatment indications. Most participants who received enoxaparin for treatment indications (76.9%) were on capping dosing regimens, which was <1 mg/kg twice daily. On the other hand, most patients (88.5%) who received enoxaparin for prophylaxis indications were on a fixed 40 mg/d dose. Among the 52 patients who completed the study, 19 patients (36.5%) had therapeutic anti-Xa levels. The results showed no statistically significant associations between regimens that were used and achieving therapeutic anti-Xa level (p>0.05). No bleeding events or thrombocytopenia were noticed, and there was one case of recurrent thrombosis. CONCLUSION: Enoxaparin dosing regimens that were used for obese patients varied based on prescribing physicians. Regardless of the regimen used, the majority of participants had nontherapeutic anti-Xa. Individualized dosing regimens based on anti-Xa levels are warranted for obese patients on enoxaparin.

Withdrawn: Novel Ternary Polymeric Blends for Controlled Release Matrices Containing Weakly Basic Model Drug.

Ahead of Print article withdrawn by publisher.

Antimicrobial activity of common mouthwash solutions on multidrug-resistance bacterial biofilms.

BACKGROUND: Periodontal bacteria occur in both planktonic and biofilm forms. While poor oral hygiene leads to accumulation of bacteria, reducing these microbes is the first step toward good oral hygiene. This is usually achieved through the use of mouthwash solutions. However, the exact antibacterial activity of mouthwash solution, especially when bacteria form biofilms, is yet to be determined. In this study, we evaluated the antibacterial activity of common mouthwash solutions against standard bacteria in their planktonic and biofilm states. METHODS: Standard bacterial strains were cultured, and biofilm were formrd. Thereafter, using standard method for determination of minimum inhibitory concentrations (MIC) values of various mouthwash solutions were determined. RESULTS: Results show that common mouthwash solutions have variable antibacterial activity depending on their major active components. Only mouthwash solutions containing chlorohexidine gluconate or cetylpyridinum chloride exhibited activity against majority, but not all tested bacterial strains in their biofilm state. Additionally, bacteria are generally less susceptible to all mouthwash solutions in their biofilm as compared to planktonic state. CONCLUSIONS: While mouthwash solutions have variable antibacterial activity, bacteria in their biofilm state pose a challenge to dental hygiene/care where bacteria become not susceptible to majority of available mouthwash solutions.

Use of first derivative of displacement vs. force profiles to determine deformation behavior of compressed powders.

Displacement (D) vs. force (F) profiles obtained during compaction of powders have been reported by several researchers. These profiles are usually used to obtain mechanical energies associated with the compaction of powders. In this work, we obtained displacement-force data associated with the compression of six powders; Avicel PH101, Avicel PH301, pregelatinized corn starch, anhydrous lactose, dicalcium phosphate, and mannitol. The first three powders are known to deform predominantly by plastic behavior while the later ones are known to deform predominantly by brittle fracture. Displacement-force data was utilized to perform in-die Heckel analysis and to calculate the first derivative (dD/dF) of displacement-force plots. First derivative results were then plotted against mean force (F') at each point and against 1/F' at compression forces between 1 and 20 kN. Results of the in-die Heckle analysis are in very good agreement with the known deformation behavior of the compressed materials. First derivative plots show that materials that deform predominantly by plastic behavior have first derivative values (0.0006-0.0016 mm/ N) larger than those of brittle materials (0.0004 mm/N). Moreover, when dD/dF is plotted against 1/F' for each powder, a linear correlation can be obtained (R2=>0.98). The slopes of the dD/dF vs. 1/F' plots for plastically deforming materials are relatively larger than those for materials that deform by brittle behavior. It is concluded that first derivative plots of displacement-force profiles can be used to determine deformation behavior of powders.

Tablet splitting and weight uniformity of half-tablets of 4 medications in pharmacy practice.

BACKGROUND: Tablet splitting is a common practice for multiple reasons including cost savings; however, it does not necessarily result in weight-uniform half-tablets. OBJECTIVES: To determine weight uniformity of half-tablets resulting from splitting 4 products available in the Jordanian market and investigate the effect of tablet characteristics on weight uniformity of half-tablets. METHODS: Ten random tablets each of warfarin 5 mg, digoxin 0.25 mg, phenobarbital 30 mg, and prednisolone 5 mg were weighed and split by 6 PharmD students using a knife. The resulting half-tablets were weighed and evaluated for weight uniformity. Other relevant physical characteristics of the 4 products were measured. RESULTS: The average tablet hardness of the sampled tablets ranged from 40.3 N to 68.9 N. Digoxin, phenobarbital, and prednisolone half-tablets failed the weight uniformity test; however, warfarin half-tablets passed. Digoxin, warfarin, and phenobarbital tablets had a score line and warfarin tablets had the deepest score line of 0.81 mm. CONCLUSION: Splitting warfarin tablets produces weight-uniform half-tablets that may possibly be attributed to the hardness and the presence of a deep score line. Digoxin, phenobarbital, and prednisolone tablet splitting produces highly weight variable half-tablets. This can be of clinical significance in the case of the narrow therapeutic index medication digoxin.