Analytical profile of the fluoroquinolone antibacterials. I. Ofloxacin

In recent years, there has been rapid progress in quinolone research and development resulting in the production of many clinically important fluoroquinolones which have been subjected to diverse analytical or assay methods. This is the first review article in this series of the fluoroquinoloneantibacterial agents with focus on the analytical profile of ofloxacin. Ofloxacin and indeed all the other fluoroquinolones are synthetic antibacterial agents structurally related to nalidixic acid. This articleexamines the synthesis, physico-chemical properties and analytical methods that have been used for the determination of ofloxacin in pharmaceutical dosages forms and biological fluids. The currentrelevant analytical trends and prospective analytical methods for ofloxacin have been presented and discussed

Optimising oral systems for the delivery of therapeutic proteins and peptides

Therapeutic proteins/peptides are mostly administered as parenteral (injectable) preparations as a result of their poor oral bioavailability which is due to degradation by proteolytic enzymes, poor membrane permeability and large molecular size. However, the oral route would be preferred to theparenteral administration because it is more convenient for   self-administration, non-invasive and more patient friendly. Consequently, efforts have intensified over the past two decades to maximize theextent of absorption of protein and peptide drugs in order to achieve optimum bioavailability via the oral route. A suitable oral delivery system should retain the drug and maintain its integrity until it gets to the region of maximum absorption where the protein/peptide is released. It would be advantageous for such a delivery system to be capable of attaching itself to the absorptive cells in that region during the course of drug release by means of specific interactions with the tissue components. Furthermore,movement of drug should be independent of prevailing factors in the gut during passage. This review examines the various efforts and strategies that have been used to pursue the goals of effective oral peptide delivery, progress made so far, as well as current trends and future prospects. Relevant issues and phenomena such as membrane permeability control, intestinal absorption, paracellular pathway and targeting have also been discussed

Transdermal delivery of bovine serum albumin using snail mucin

The study aimed at evaluating the bioadhesion properties and penetration enhancing effect of mucin-based bovine serum albumin (BSA) transdermal patches. Mucin was extracted from the giant African snail Archachatina maginata by differential precipitation with acetone and alum. Various batches of BSA loaded transdermal film patches were prepared with the precipitated mucin and varying volumes (0, 0.2 and 0.5 mL) of polyethylene glycol (PEG) as plasticizer. Prepared patches were evaluated for weight uniformity, patch thickness, folding endurance, moisture content and uptake, bioadhesion, drug content and in vitro and ex vivo diffusion studies. Differential scanning calorimetry analysis showed no interaction between BSA and mucin. Mean weight range from 0.11±0.02 to 0.13±0.05 g, moisture content (32 %) and moisture uptake was highest with patches prepared with acetone-precipitated mucin (up to 129 %) and decreased as PEG concentration increased. All the patches showed bioadhesion values between 1.70 - 1.98 g/sec. Drug diffusion across treated rat skin was 47 % after 12 h from patches prepared from acetone-precipitated mucin. Thus, snail mucin showed promise as a transdermal drug delivery base in the formulation of BSA patches because of its bioadhesion property and penetration enhancing effect.Keywords: Bioadhesion, drug diffusion, proteins, mucin, transdermal deliver

Investigation of the Effect of Alkali Modification of Mucin on Some Properties of Metronidazole Bioadhesive Tablets

The objective of this study was to investigate the effect of alkali treatment of mucin on the mucoadhesive properties and tablet parameters of metronidazole tablets. Mucin was extracted from the African giant snails (Archachatina maginata) by differential precipitation using acetone, air-dried and pulverized. Different portion of the mucin powder was treated with mineral bases (sodium and ammonium  hydroxides) and organic base (pyridine) at high and low concentrations and at varied times of 1 and 12 h. Ten batches of metronidazole tablets (B1-B10) were prepared with the modified mucin by direct  compression. Their granules and tablets were evaluated for flow properties and tablets parameters,  respectively. Tablet mucoadhesion was determined using the mass flow rate method. All the  batches of granules gave good flow characteristics with their angles of repose < 30°. The formulated tablets passed the weight variation test and had hardness  values within the range of 3.2 to 5.0 kp and friability of 0.7 to 2.0 % while the content of active drug met official compendial requirements. Tablets of 1 M NaOH  treated mucin for 1 h gave the best mucoadhesion values of 5.95 g/sec, followed by the 0.1 M NaOH 12 h treatment and 0.1 M NaOH 1 h treatment with 4.34 g/sec and 4.14 g/sec, respectively. These values  were higher than those of the unmodified mucin tablets which gave 0.75 g/sec. Tablets of 0.1M pyridine treated mucin for 1 h gave the least mucoadhesion values of 0.51 g/sec. Tablets of mucin treatment using NaOH gave improved mucoadhesive properties compared to the  unmodified mucin. Thus, NaOH modified mucin can be preferred in the formulation of some mucoadhesive dosage forms.Keywords: alkali treatment, mucin, mucoadhesion, tablets, metronidazole

Some Physical Properties of Vernonia amygdalina and Garcinia kola Microspheres Prepared with High Molecular Weight Polyethylene Glycols

The effect of polymer concentrations on some of the physicochemicalproperties of Vernonia amygdalina (Linn) and Garcinia kola (Heckel) extracts loaded microspheres was evaluated. Microspheres of the aqueous extracts was prepared by emulsion solvent evaporation using polyethylene glycol (PEG) mixtures of molecular weight 4000 and 6000 at different ratios of 1:0, 0:1, 1:1, 1:2 and 2:1 while the amounts of the extracts incorporated was constant for all ratios. The microspheres were evaluated for their particles sizes, yield, flavonoid content, loading efficiency, moisture loss and flow properties. In-vitro release studies were carried out by monitoring flavonoid release rate from the microspheres. The  microspheres were spherical and uniformly shaped and exhibited good flow characteristics. Their size range, yield, loading efficiency, moisture loss and flavonoid content were 76 - 83 ìm, 49 - 76 %, 47 - 82 %, 2.18 - 4.60 % and 17.10 - 23.80 mg%, respectively for V. amygdalina and 144 - 160 ìm, 50 - 68 %, 51 - 68 %, 3.00 - 4.41 % and 20.00 - 28.70 mg%, respectively for G. kola. Flavonoids release from the microsphere was up to 90 % within 1 h and it followed a matrix release kinetic model with a super  case-II transport mechanism. The concentrations of the polymers affected the yield, loading efficiency, moisture loss and the extent of flavonoid release of the microspheres but had no effect on their particle sizes and flavonoid content. These results may find useful application in the delivery of V. amygdalina and G. kola extracts since the combination of PEG of different molecular weights resulted in microspheres with good physicochemical and release properties. © JASE

In Vitro Assessment of Quality Control Parameters of Some Commercially Available Generics of Amlodipine Besylate in Nigerian Drug Market

Purpose: To use specific parameters to evaluate the in vitro quality assurance of ten generics of amlodipine besylate (10mg) tablets commonly sold in the Nigerian drug market. Methods: Organoleptic and physicochemical properties of 10 brands of the amlodipine besylate tablets were assessed according to official and unofficial standards. Basic quality control parameters evaluated include uniformity of weight, uniformity of content, tablet friability, hardness test, disintegration and dissolution tests. Results: The results show that all the tablets passed the weight uniformity (mean tablet weights ranging from 155±003mg to 404±0.002 mg), friability < 5%, disintegration (< 4 mins) and dissolution tests (>70% released within 40 mins). While seven of the ten brands passed the uniformity of content, two out of the three brands that failed the test were unregistered by NAFDAC. The seven brands can be used interchangeably with the branded, Amlovar®. Conclusion: The finding of this research further underscores the need for stakeholders and end users to insist on the use of only duly registered products by the regulatory body.Keywords: Amlodipine besylate, control parameters, generics

Effect of Solvent Type and Drying Method on Protein Retention in Chitosan-Alginate Microcapsules

Purpose: The effect of solvent used in dissolving chitosan (membrane material) and the microcapsule drying method used, on protein retention in chitosan-alginate microcapsules were studied since these factors affect the physicochemical characteristics of the coating membrane. Method: The microcapsules were prepared by extruding a solution containing alginate and BSA into chitosan/calcium chloride solution prepared with different acid solvents – acetic acid, formic acid, tartaric acid and hydrochloric acid. A portion of the microcapsules was air-dried at ambient temperature while the remaining portion was freeze-dried. The elution of protein from the microcapsules in simulated gastric fluid was monitored spectrophotometrically at λmax 280 nm. Results: Tartaric acid effected the highest mean protein retention (54%) after 9 h followed by acetic acid (35%), hydrochloric acid (31%) and formic acid, (30%). There appears to be a link between the pKa of the acids and the degree of chitosan–solvent interaction on the one hand, and protein retention on the other hand. Increase in elution pH from 1.2 to 5.0 did not significantly (P>0.05) affect protein retention. Furthermore, there was no significant difference (p>0.05) between the protein retention capacities of air-dried and freeze-dried microcapsules as both types showed protein retention of 50% after 5 h. Conclusion: Tartaric acid was the most suitable solvent for enhancing protein retention in chitosan-alginate microcapsules in simulated gastric fluid . Keywords: Tartaric acid, chitosan, solvent type, microcapsules, air-drying, freeze-drying.> Tropical Journal of Pharmaceutical Research Vol. 5 (2) 2006: pp. 583-58

PRELIMINARY INVESTIGATION OF THE MUCOADHESIVE PROPERTIES OF THERMALLY MODIFIED MUCIN ON METRONIDAZOLE TABLETS

Objective: To determine the effect of thermal treatment of mucin on the mucoadhesive and tablet parameters of metronidazole tablets. Methods: Mucin was extracted from the giant African snails (Archachatina maginata) by differential precipitation using acetone, air-dried and pulverized. Modification of the mucin powder was carried out using a regulated water bath at 60 and 100 °C and at varied times of 1 and 12 h and a micro-wave oven at varied wattage (100-600 W) and time. Ten batches of metronidazole tablets (A1-A10) were prepared with the modified mucin by direct compression. Their granules were evaluated for flow properties and the tablets for weight uniformity, crushing strength, friability, drug content and in vitro studies. Tablet mucoadhesion was determined using the mass flow rate method. Results: Granules of all the batches exhibited good flow characteristics with their angles of repose<30 °. Tablets formulated passed the weight variation test with hardness values above 4.0 kp and friability of 1.10-1.85 % while the content of active drug met official compendial requirements. Tablets of treated mucin at 60 °C for 1 and 12 h gave mucoadhesion values of 1.80 g/sec This value was higher than those of the unmodified mucin tablets which gave 0.70 g/sec. Tablets of micro-wave treated mucin gave mucoadhesion values of 1.0-1.30 g/sec, which were also higher than that of the unmodified mucin Conclusion: The study shows that modification of mucin at 60 °C for 1 and 12 h may be considered as the most promising among the batches tested as their tablets had improved mucoadhesive properties compared to the unmodified mucin

Simplex lattice optimization of superdisintegrants in the formulation of fast oral dissolving tablets of ibuprofen

Optimization of different superdisintegrants using the simplex lattice design in the formulation of fast disintegrating tablets of ibuprofen was studied. Seven formulations (F1 to F7) were prepared by direct compression of ibuprofen as the model drug and a combination of superdisintegrants–pre-gelatinized starch, croscarmellose sodium and crospovidone–utilizing the simplex lattice design. FTIR analysis of drug and excipients was carried out. Granules and tablets formulated were evaluated for pre- and post-compression parameters. The granules were fairly free flowing with angles of repose ranging from 42 - 49°, Carr’s index < 24 %, and a Hausner’s quotient < 1.3. The tablet hardness and friability were 4.00 - 5.99 kgF and < 1 %, respectively, while wetting and disintegration times were < 160 and < 76 s, respectively. Dissolution profiles showed all the tablets released over 60 % of drug within 5 min. FTIR analysis showed no interactions between ibuprofen and excipients. The simplex lattice design revealed that combination of superdisintegrants significantly affects the wetting and disintegration times as well as drug release.Keywords: Simplex lattice, fast disintegrating tablets, superdisintegrant

Molecular characterization of selected nasal isolates of methicillin-resistant Staphylococcus aureus (MRSA) from healthy students of a tertiary institution

Purpose: To investigate the incidence of methicillin-resistant Staphylococcus aureus (MRSA) and carry out molecular characterization in selected nasal isolates from healthy students in Abraka, Nigeria.Methods: Three hundred (300) samples were obtained from apparently healthy 150 female and 150 male students and were cultured in suitable media for identification. The MRSA were detected by means of oxacillin antibiotic sensitivity disk. Antibiotics susceptibility pattern of MRSA isolates was carried out in accordance with the guidelines of Clinical Laboratory Standard Institute. Tests were carried out to determine the presence of penicillin binding protein2a (PBP2a). Molecular characterization of twenty (20) MRSA representatives was done to establish the existence of the mecA genes among the isolates.Results: The incidence of MRSA colonization amongst apparently healthy students in the community was 68 (22.7 %). The sensitivity pattern was: amoxicillin, 40 (58.8 %); amoxicillin/clavulanate, 15 (22.1 %); chloramphenicol, 15 (22.1 %); ciprofloxacin, 19 (27.9 %); co-trimoxazole, 9 (13.2 %); gentamicin, 9 (13.2 %); ofloxacin, 8 (11.1 %); and streptomycin, 30 (44.1 %). All the twenty (20) isolates subjected to molecular characterization possessed penicillin binding protein2a (PBP2a) while only one possessed the mecA gene.Conclusion: The MRSA is present among healthy individuals in Abraka, Delta State. It is also possible not to detect the existence of the mecA gene even when penicillin binding protein2a is present. Since most of the MRSA isolates are multi-drug resistant, there is a tendency for clinical antibiotic therapy failure in this area