KNH-UoN Ethics and Research Committee

No Abstract!

No Abstract!

HIV/AIDS has become one of the major and deadliest pandemics in the world today. Besides
concerns about cost and accessibility, a major concern for current therapies in most
developing countries is the lack of age appropriate antiretroviral formulations which might
expose children to "homemade" formulations with significant risks of variable dosing, poor
and erratic absorption and inappropriate pharmacokinetic profiles. In this light and with the
several campaigns driven by the World Health Organisation (WHO), UNICEF and the
European Medicines Agency (EMA) in mind, the potential for developing alternative
presentations for paedratic use has been raised. Flexible options such as granules, pellets,
mini- matrices which children are able to swallow or which can be dispersed on the tongue or
in water have been identified as the presentations of choice in some of these WHO led
discussions. It is therefore critical that feasibility assessments are undertaken to demonstrate
the likelihood of administrating essential medicines in this manner. In this regard, two
antiretroviral drugs have been identified for this study. Oral zidovudine (AZT) and
lamivudine (3TC) are soluble drugs with short elimination half-lives and moderate
bioavailability. Free high doses are therefore required to achieve and maintain
therapeutic blood. As a result, dose-dependent toxic side effects are frequently
observed. One way to avoid dependent side effects is by formulating the dosage forms
as sustained release formulations intended to optimize a therapeutic regimen by providing
slow and continued service delivery over the entire dosing giving reduced side effects, whilst
also providing compliance and convenience. To have access and availability of
paediatric fixc : iSC bination mini matrices at low cost, a fast, flexible and efficient
manufacturing process which can be adapted by local manufacturers in HIV/AIDS endemic
regions such .: ; 'an African is required. One-such process that could be adapted and
scaled up for: .ctic .isily is hot melt extrusion (HME).

This study was therefore designed to investigate the physicochemical properties of
zidovudine and lamivudine and their influence on interactions with matrix forming polymers
such as ethylcellulose, Polyvinylpyrrolidone/Vinyl acetate (Kollidon® SR) and polyethylene
oxide (PEG) during hot melt extrusion. Furthermore, mini-matrix formulations of fixed dose
combinations of zidovudine and lamivudine were developed followed by evaluation of key
quality attributes including in-vitro dissolution and accelerated stability studies. The
dissolution data were used to make estimations of in-vivo performance using a method
described in the literature.
The results showed that Zidovudine and Lamivudine were thermally stable and miscible (Van
Krevelen's solubility parameter calculations) with polymers such as ethylcellulose, Kollidon®
SR and PEG enabling extrusion by hot melt extrusion. Thermal and crystalline characteristics
were studied using Differential Scanning Calorimetry (DSC) and X-ray powder diffraction
studies (XRPD) which showed that the drugs were transformed from the crystalline to the
amorphous state. Rheological studies showed that addition of Zidovudine decreased the melt
viscosity with all the polymers while Lamivudine seemed to saturate the polymer at 40%w/w
concentration at which point there was a marked increase in melt viscosity. Triethyl citrate
(TEC) was used as plasticizer during hot melt extrusion, whilst polyethylene oxide (PEG)
was added to modulate the drug release profile. For some formulation variants, extensive drug
release (98%) was observed over a period of .24 hrs, particularly for mini-matrices of
zidovidine and lamivudine formulated with Kollidon® SR. The release was related to the
increases in percentage of plasticizer TEC which may have caused strong coalescence
between the drug and polymer particles. Accelerated stability studies done using mini
matrices in open and closed high density polyethylene (HDPE) bottles for a period of three
month in a hot oven chamber at 40° C and 75% Relative Humidity (RH) as well as at 60°C in
Humidity (RR) as well as at 60°C in closed HDPE bottles for 15 days and the results showed
that the both zidovudine and lamivudine did not recrystallized and the matrices were stable
after 3 months. The data obtained from the predicted in vivo drug blood concentration profiles
for ethylcellulose and Kollidon® SR formulations showed that both zidovudine and
lamivudine not only sustained drug release for over 16 hrs but also maintained drug
concentration within the effective drug concentrations (therapeutic window) over the same
period which suggests that side effects caused by frequent dosing of the drugs could be
avoided.
In conclusion, it is feasible to produce stable fixed dose combination sustained release mini
matrices of zidovudine/lamivudine using HME with ethylcellulose, Kollidon® SR and PEO.
This platform therefore provides potential to be used a standard method for producing
sustained release formulations of antiretroviral drugs for use in the paediatric population.

No Abstract!

To estimate the prevalence and pattern of substance use among children and young persons appearing in the Nairobi Juvenile Court, Kenya. DESIGN: A point prevalence survey. SETTING: The Nairobi Juvenile Court, Kenya. SUBJECTS: Ninety (sixty four males and twenty six females) children and young persons aged 8 to 18 years classified as criminal offenders, group I (60) and those for protection and discipline, group II (30), were selected. METHOD: Socio-demographic and substance use questionnaires were administered to the subject. International classification of diseases, 10th Edition (ICD-10) diagnostic criteria were used. RESULTS: Crude rate for substance use in this study was found to be 39 out of the total sample of 90(43.3%), children and young persons. Of these thirty nine, 33 (85.8%) were males and six(14.2%) were females. Twenty nine (32.2%) used nicotine, 19(21.1%) used volatile hydrocarbons, 8(8.9%) used cannabis six (6.7%) used alcohol, five (5.6%) used khat and three (3.3%) used sedatives. Multiple substance use was also evident. CONCLUSION: This study has shown a high presence of substance use in children and young persons appearing in the Nairobi Juvenile Court.

To estimate the prevalence and pattern of psychiatric disorders among children and young persons appearing in the Nairobi juvenile court, Kenya. DESIGN: A point prevalence survey. SETTING: The Nairobi Juvenile Court, Kenya. SUBJECTS: Ninety (sixty-four males and twenty-six females) children and young persons aged 8 to 18 years classified as criminal offenders, group I (60), and those for protection and discipline, group II (30), were selected. METHOD: A socio-demographic questionnaire, reporting questionnaire for children (RQC), follow-up interview for children (FIC), present state examination (PSE) and clinical interview were administered to the subjects. International Classification of Diseases, 10th Edition (ICD-10) diagnostic criteria were used. RESULTS: The crude psychiatric morbidity (CPM) rate was 44.4%. ICD-10 documented psychiatric disorders detected in those with CPM were conduct disorders 45%, mixed disorders of conduct and emotion 20%, emotional disorders with onset specific to childhood 20%, mood disorders 12.5% and hyperkinetic disorders 2.5%. CONCLUSION: This study has shown a high presence of psychiatric morbidity in children and young persons appearing in the Nairobi Juvenile Court. These juveniles need and would benefit from mental treatment as recommended in section 18 of Cap 141 of the laws of Kenya; The Children's and Young Persons Act