Plasmodium falciparum malaria in pregnancy: prevalence of peripheral parasitaemia, anaemia and malaria care-seeking behaviour among pregnant women attending two antenatal clinics in Edo State, Nigeria.

SUMMARY: This study evaluated malaria care-seeking behaviour, as well as the prevalence of parasitaemia and anaemia among pregnant women attending antenatal clinics of two tertiary healthcare facilities in Edo State, Nigeria. Malaria was highly prevalent in the study group (20% by microscopy and estimated 25% by PCR), but parasitaemia and incidence decreased with increasing number of pregnancies. Although the level of education of the study participants was relatively high, antimalarial control measures during pregnancy were found to be poorly utilised by the women and malaria care-seeking was often delayed. A minority of the interviewed pregnant women said they had received sulphadoxine/pyrimethamine-based intermittent preventive therapy (IPT) during current pregnancy. Moreover, the use of inferior antimalaria treatment (e.g. chloroquine) was frequent. The majority of the pregnant women, mainly primigravidae, were anaemic. Efforts to improve antimalaria healthcare must be intensified, targeting pregnant women, particularly the primigravidae and secundigravidae and the healthcare providers.

"A Study of the Pharmaceutical Quality of Chloroquine and Paracetamol Products Sold in a Major Nigerian ""Market"""

"Malaria is a major public health problem in endemic countries; and the quality of anti-malarial products is a concern in the therapeutic management of individual patient. In this study; we have evaluated the pharmaceutical quality of chloroquine and paracetamol oral products obtained from a major Nigerian drug ""market"" using a less elaborate sampling procedure. Results have shown that there are still some defects in the pharmaceutical quality of these drugs; despite the activities of the Nigeria's drug regulatory agency (National agency for Food and Drug Administration and Control; NAFDAC). 21(7/34) of the drug products were not registered by NAFDAC. The pharmaceutical properties of the products indicated that 6; 15; 9; and 9of them failed tests for disintegration; dissolution; crushing strength; and percentage of active content; respectively. 4 out of the 6 chloroquine liquid preparations evaluated had inadequate active content. These defects could have resulted from deliberate counterfeiting; poor quality control during manufacture or decomposition of the products. However; this could not be ascertained from the data available to us in this study. The implication of these findings; however; is that the newer anti-malarial drugs that have recently been introduced into the Nigerian market should be safeguarded; if their therapeutic usefulness must be sustained."

Review Article - An Overview of Pharmaceutical Validation and Process Controls in Drug Development

It has always been known that facilities and processes involved in pharmaceutical production impact significantly on the quality of the products. The processes include raw material and equipment inspections as well as in-process controls. Process controls are mandatory in good manufacturing practice (GMP). The purpose is to monitor the on-line and off-line performance of the manufacturing process; and hence; validate it. Thus validation is an integral part of quality assurance. This overview examines the need for pharmaceutical validation; the various approaches and steps involved; and other pertinent considerations

Prescribing Practices in two Health Care Facilities in Warri; Southern Nigeria : a Comparative Study

PURPOSE: Inappropriate prescribing has been identified in many health facilities in developing countries. The purpose of this study was to evaluate the prescribing practices in two health care facilities in Warri located in south-south geopolitical region of Nigeria and identify factors influencing the practices. METHOD: WHO Prescribing Indicators were applied to evaluate 2000 prescription records; retrospectively; from a private and a public hospital in Warri. Factors influencing the prescribing practices in the facilities were identified through informal interviews of 10 prescribers in the facilities. Using a self-administered questionnaire administered to 40 prescribers in the facilities; we also evaluated the order of importance of the factors affecting drug prescribing. RESULTS: Average number of drugs per encounter in the health facilities is 3.4 (3.9 in the public hospital and 2.8 in the private hospital). Generic prescribing was generally low (54 percent in the public hospital and 16 percent in the private hospital) while the percentage of encounters with antibiotics prescribed was high (75 percent in the public hospital and 55 percent in the private hospital). Antimalarials; antihypertensives; antidiarrhoeals and analgesics accounted for 47.4 percent; 7.5 percent; 1.0 percent and 18.2 percent; respectively. The overuse of drugs and generic prescribing were significantly lower in the private hospital than in the public hospital. Major factors influencing prescribing practices included drug availability; clinician's level of training; cost of drugs; feedback from patients and socio-economic status of patients. CONCLUSION: Polypharmacy; overuse of antibiotics and low rate generic prescribing still occur in the health facilities studied. Drug availability; clinician's level of training; cost of drugs; feedback from patients and socio-economic status of patients are major factors influencing prescribing in the facilities

Modulation of protein release from chitosan-alginate microcapsules using the pH-sensitive polymer hydroxypropyl methylcellulose acetate succinate.

The release characteristics of protein from chitosan-alginate microcapsules prepared using an electrostatic droplet generator were evaluated. The release studies were undertaken in-vitro in simulated gastrointestinal fluids covering the pH range 1.2-8. Chitosan-alginate microcapsules showed unsatisfactory release properties, losing 94% of the encapsulated proteins (bovine serum albumin) over a 24 h period at pH 1.2. Incorporation of a pH-sensitive polymer, hydroxypropyl methylcellulose acetate succinate (HPMCAS), in the microcapsules, by coating the capsule membrane as well as blending with the capsule core polymer in varying ratios, produced significant changes in the release profiles of the microcapsules. At pH 1.2, the modified microcapsules retained up to 60% of the encapsulated protein after 24 h. The results obtained highlight the potential of HPMCAS as a release-modifier in chitosan-alginate microcapsules.

Influence of oral co-administered metallic drugs on ofloxacin pharmacokinetics.

Following recent concern over probable interactions between the 4-quinolones and metal ions, the effect of co-administered drugs--sodium bicarbonate, potassium citrate, ferrous sulphate, magnesium trisilicate, calcium carbonate and aluminium hydroxide--on the saliva and urine pharmacokinetics of ofloxacin in healthy human volunteers has been investigated. The Cmax and AUC0-9 in saliva were generally in the range 1.05-1.40 mg/L and 4.89-6.16 mg.h/L, respectively, and were unaffected (P less than 0.05) by the metallic drugs, except aluminium hydroxide which lowered these values. Again, only aluminium hydroxide modified the Ka of ofloxacin, resulting in a slower absorption rate. However, none of the metallic drugs altered the T1/2 beta of the 4-quinolone in saliva. In-vitro studies using simulated gastric fluid showed that ferrous sulphate, aluminium hydroxide and calcium carbonate reduced ofloxacin availability to 67.4%, 69.3% and 73.8%, respectively. This effect was ascribed to the formation of complexes between ofloxacin and the metal ions concerned. Substantial correlation between in-vitro and in-vivo availability data was demonstrated in all cases except for ofloxacin combinations with ferrous sulphate and calcium carbonate. In general, there was also good correlation between the saliva and urine data.

Thermal characterization of drug/polymer and excipient/polymer interactions in some film coating formulation.

Some probable consequences of the dissolution/migration of a major solid dosage component in or into an applied film coating during or after a film coating operation have been investigated using free films of hydroxypropyl methylcellulose (HPMC) and polyvinyl alcohol (PVA) incorporating small amounts of either lactose (a diluent) or ephedrine hydrochloride (a drug). Intrinsic features of the films such as softening, glass transition, crystallinity and melting were examined by differential scanning calorimetry and thermomechanical analysis. Generally, the results indicate that ephedrine hydrochloride exhibited plasticizing activity in both HPMC and PVA films. On the other hand, incorporation of lactose produced an opposite effect (stiffening) in PVA films as demonstrated by increased glass transition temperature and crystallinity. On the basis of these findings, it was proposed that the undesired presence of a component of a solid dosage core in the applied film coating could significantly alter its end-use properties such as diffusivity and the incidence of film coating defects. It was also shown that the application of the relationship of Moelter & Schweizer (1949) in the evaluation of the plasticizer efficiency of non-homologous additives could pose problems of interpretation.

Studies of interaction phenomena in aqueous-based film coatings containing soluble additives using thermal analysis techniques.

Interaction phenomena, in aqueous-based hydroxypropyl methylcellulose (HPMC) and polyvinyl alcohol (PVA) film-coating formulations containing water-soluble additives (citric acid and urea) have been examined by thermal methods to assess glass transition, softening, melting, plasticization, and crystallinity. The methods used were differential scanning calorimetry (DSC) and thermomechanical analysis (TMA) in penetration and expansion modes. In addition to the established thermal transitions occurring in HPMC and PVA at relatively high temperatures, transitions were also observed between 26 and 43 degrees C using TMA. These low temperature transitions, unlike those occurring at the higher temperatures, were low energy transitions and not influenced by the type and concentration of the additives incorporated. The results also showed that the plasticizing activities of citric acid and urea were as high as those of some currently used plasticizers. On a weight basis, urea was superior to citric acid as a plasticizer for either HPMC or PVA, but when their molar contents were considered, the position was reversed. Also, PVA crystallinity was depressed in the presence of the additives.

Moisture permeability mechanisms of some aqueous-based tablet film coatings containing soluble additives.

Moisture permeation parameters--diffusion, solubility and permeation coefficients--for hydroxypropyl methylcellulose (HPMC) and partially hydrolyzed polyvinyl alcohol (PVA) films containing either of two water-soluble additives (citric acid and urea) have been evaluated from transmission and time lag data. Contrary to expectations, the moisture diffusivities of the films were markedly lowered by the presence of these additives. However, the solubility coefficients increased while the permeability coefficients were largely unchanged up to 10 wt% of the additives. A complex phenomenon involving an extensive interlacing network of mainly hydrogen bond interactions between additive and films former was believed to influence the permeation properties of the films. The estimated limits of compatibility of the additives with the film-former were in the range of 5-10 wt%.

Mechanical properties of some pigmented and unpigmented aqueous-based film coating formulations applied to aspirin tablets.

The Brinell hardness and Young's modulus of pigmented and unpigmented films of hydroxypropyl methylcellulose alone, and in combination with either polyethylene glycol 400 (plasticizer) or polyvinyl alcohol, which were applied to aspirin tablets, have been measured. Generally hardness and modulus data showed similar trends. The hardness and modulus of hydroxypropyl methylcellulose fell in the presence of polyethylene glycol 400 as a result of its plasticizing action. On the other hand, the hardness and modulus of the film former rose slightly when polyvinyl alcohol was initially incorporated, probably due to the crystalline phase of the additive, and then decreased when the level of the additive was further raised. Hardness and modulus were higher in films pigmented with talc than in those containing titanium dioxide because of the plate-like shape of talc and its greater interaction with the polymer systems. Some correlation was found between the Young's moduli of the applied films and those of the corresponding free films, with the moduli of the latter two 2-5 times greater. Ageing at 37 degrees C and 75% r.h. was found to cause a decrease in the mechanical properties of the unplasticized film coating systems probably as a result of decreased molecular order and enhanced polymer chain mobility.

The adhesion characteristics of some pigmented and unpigmented aqueous-based film coatings applied to aspirin tablets.

The adhesion of pigmented (with talc and titanium dioxide) and unpigmented aqueous-based films, derived from hydroxypropyl methylcellulose, to aspirin tablets and the effect of ageing on the measured adhesion have been assessed. The adhesion of hydroxypropyl methylcellulose film attained maximum values at polyethylene glycol 400 and polyvinyl alcohol levels of 10 and 20 wt%, respectively. Above these concentrations, adhesion decreased. For solid loaded films it is proposed that the effect of pigments on film adhesion is dependent on the balance between their influence on the internal stress of the film coating and the strength of the film-tablet interface. Adhesion was enhanced when a pigment increased the strength of the interface faster than it increased internal stress, and vice versa. A simple relation between the measured adhesion and the incidence of edge splitting of film-coated tablets was not observed. Generally, film adhesion fell when the tablets were aged at 37 degrees C and 75% r.h. as a result of swelling-induced stresses in the film and at the film tablet interface. The effect of ageing on the adhesion of the system plasticized with polyethylene glycol 400 was eased when the film was pigmented. Adhesion was largely unaffected with film-coated tablets stored in tightly closed bottles at 20 degrees C for five months.

Stress crack resistance of some pigmented and unpigmented tablet film coating systems.

Stress crack resistance parameters--tensile strength: Young's modulus ratio, relative surface energy, and toughness index--have been examined for unpigmented free films of hydroxypropyl methylcellulose containing polyvinyl alcohol, and polyethylene glycols 400 and 1000, as well as similar film systems pigmented with either talc or titanium dioxide. Incorporation of either polyvinyl alcohol or polyethylene glycols 400 and 1000 in hydroxypropyl methylcellulose film coatings eliminated the incidence of edge splitting in the coated tablets. Increase in pigment concentration generally led to a decrease in the crack resistance of pigmented films. There was a relation between the stress crack resistance of pigmented free films and the incidence of edge splitting of corresponding film coatings applied to aspirin tablets--generally, the higher the crack resistance the lower the incidence of edge splitting. A similar relationship applied to the unpigmented films only when the tensile strength: Young's modulus ratio was considered.

Tensile anisotropy of some pigmented tablet film coating systems.

The tensile properties of representative tablet film coating systems, containing hydroxypropyl methylcellulose alone and in combination with either polyvinyl alcohol, polyethylene glycol 400 and polyethylene glycol 1000 and pigmented with either talc or titanium dioxide, have been investigated. Tensile anisotropy was observed between film samples cut parallel to, and perpendicular to, the direction of rotation of the casting substrate and factors accounting for this phenomenon are presented.

Characterization of moisture interactions in some aqueous-based tablet film coating formulations.

Three methods--radiotracer, differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA)--have been employed to evaluate moisture interactions in aqueous-based hydroxypropyl methylcellulose films containing polyethylene glycol 400, polyethylene glycol 1000 or polyvinyl alcohol. The radiotracer employed was tritiated water. Using a proposed classification, the water present in the films was placed in three categories: tightly bound, moderately bound and free. The tightly bound water in hydroxypropyl methylcellulose and hydroxypropyl methylcellulose/polyvinyl alcohol films was related to the crystallinity of the films whilst tightly bound water was practically non-existent in the plasticized systems thus indicating the absence of crystallinity. Free (or freezable) water could not be detected in the films using DSC. The moisture content data obtained by TGA were considered to represent moderately bound water. The moderately bound water content of the film systems was in the rank order of the hydrophilicity of the polymer additives: polyethylene glycol 400 greater than polyethylene glycol 1000 greater than polyvinyl alcohol. This order was reversed for the calculated free water content.

Interaction Phenomena in some Aqueous-Based Tablet Coating Polymer Systems.

Molecular interactions in aqueous-based tabletfilm coating systems consisting of hydroxypropyl methylcellulose (HPMC) in combination with either polyvinyl alcohol (PVA), polyethylene glycol (PEG) 400 or PEG 1000 have been investigated by viscometry and thermal analysis. The viscosity results indicate that the solvent (water) inhibited polymer-polymer interaction and this inhibitory effect was directly related to the solvent affinity of the polymer additive. The presence of crystallinity in the films was examined using a differential scanning calorimeter (DSC). HPMC/PVA blends were partially crystalline but the plasticized HPMC films showed no signs of crystallinity. Glass transition data were also obtained with the DSC. The plasticizer effects of PEG 400 and PEG 1000, respectively, in HPMC were confirmed by the fall in the glass transition temperature (Tg) of HPMC. On the other hand, incorporation of PVA increased the Tg of HPMC, and this was attributed to the presence of a crystalline phase in the blend. Maximum compatibility levels of PVA, PEG 400 and PEG 1000 in the polymer blends were found to be 40, 20 and 15 wt %, respectively, based on glass transition data.

Analysis of the permeation and mechanical characteristics of some aqueous-based film coating systems.

The moisture permeability and mechanical properties of some aqueous-based free films have been evaluated using sorption-desorption and stress-strain techniques, respectively. These properties for blends of two film-formers--hydroxypropyl methylcellulose and polyvinyl alcohol--have been compared with those of hydroxypropyl methylcellulose films plasticized with polyethylene glycols. The polyethylene glycols generally increased the moisture permeability of hydroxypropyl methylcellulose films while polyvinyl alcohol decreased it. Both polyvinyl alcohol and the polyethylene glycols lowered tensile strength at break and Young's modulus but the effects of the polyethylene glycols were more pronounced. These results are discussed in terms of structural interactions between film components. All film systems evaluated, except that containing hydroxypropyl methylcellulose alone, exhibited a degree of anisotropy, a phenomenon with potentially adverse consequences in tablet film coating.