Group Research Articles

1. In vitro evaluation of the quality of essential drugs
on the Tanzanian market
Peter G. Risha1
, Danstan Shewiyo2
, Amani Msami2
, Gerald Masuki2
, Geert Vergote3
, Chris Vervaet3
Lungwani MuungoT. and Jean Paul Remon3
1 Department of Pharmaceutics, Faculty of Pharmacy, Muhimbili University College of Health Sciences, Dar es Salaam, Tanzania
2 Ministry of Health, Dar es Salaam, Tanzania
3 Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Ghent University, Belgium
Summary We evaluated the in vitro availability and its stability under simulated tropical conditions of various
formulations of four essential drugs marketed in Tanzania. We obtained 22 formulations (containing
paracetamol, acetylsalicylic acid, chloroquine or sulphadoxine/pyrimethamine) from wholesale
pharmacies in Dar es Salaam and the Medical Stores Department (Tanzania). The drug content, in vitro
availability (dissolution) and its stability under simulated tropical conditions were determined using
methods specified in the United States Pharmacopoeia (USP) 24 monograph of the respective drugs. All
formulations passed the pharmacopoeia requirements for the drug content. However, seven
formulations (three acetylsalicylic acid, two sulphadoxine/pyrimethamine and two paracetamol) failed
to meet the USP 24 tolerance limits for dissolution. Another five formulations (three paracetamol and
two chloroquine) failed to meet the dissolution tolerance limits after being subjected to an accelerated
stability test under simulated tropical conditions (75% RH/40 °C) for 6 months. The study has
demonstrated the presence on the Tanzanian market of essential drug formulations that met potency
requirements and yet had unsatisfactory in vitro availability as they were not robust enough to withstand
storage under simulated tropical conditions.
keywords Tanzania, essential drugs, drug quality, dissolution, stability
correspondence Prof. Dr Jean-Paul Remon, Laboratory of Pharmaceutical Technology, Harel-
bekestraat 72, 9000 Ghent, Belgium. Fax: +32 0 9 222 82 36; E-mail: jeanpaul.remon@rug.ac.be
Introduction
In 1975, the WHO passed a resolution (WHO 28.66) that
marked the birth of the Essential Drugs Concept. Its most
important component is the recognition of the fact that
only some drugs are necessary for the treatment, diagnosis
and prophylaxis of diseases facing the majority of people in
a community. Essential drugs have the potential to reduce
morbidity and mortality from common illnesses for
millions of people in the developing countries where medi-
cines are unaffordable, unavailable, improperly used or of
poor quality. The main pillars of the Essential Drugs
Concept are: established safety and efficacy, proven qual-
ity, constant availability, affordability and rational use.
The Government of Tanzania through the Ministry of
Health has adopted the Essential Drugs Concept in its
National Drug Policy. Amongst the objectives of this policy
is to make available at all times essential drugs (of proven
quality, safety and efficacy) at prices affordable to the
community and the promotion of the rational use of drugs.
Studies done in Tanzania using the International Network
for Rational Use of Drugs indicators have shown that much
success has been achieved in the area of rational drug use
(Gilson et al. 1993; Massele & Mwaluko 1993). The
WHO has categorized Tanzania as a country where the
essential drugs list exists and is used in all aspects of drug
management (WHO 1988).
While much success has been achieved in the area of
rational drug use, not much information is available
concerning the quality of the essential drugs on the
Tanzanian market. There are several reports on the
presence of substandard drugs on market in other
developing countries (Kibwage et al. 1992; Shakoor et al.
1997; Taylor et al. 2001). In Tanzania, which imports
more than 80% of its drug needs from various countries,
the drug distribution system has recently been liberalized
Tropical Medicine and International Health
volume 7 no 8 pp 701–707 august 2002
ª 2002 Blackwell Science Ltd 701
3

2. and operates on a market-orientated demand system. The
combination of market forces, the low per capita spending
on pharmaceuticals by most of the population and the lack
of adequate resources for controlling and monitoring the
quality of drugs on the market creates an environment
favourable for introducing low quality drugs. Moreover,
the tropical climatic conditions (high temperature and
humidity) may alter the quality of drugs during distribution
and storage. This study was undertaken to provide detailed
information on the quality (drug content, in vitro avail-
ability and stability) of four essential drugs (chloroquine,
sulphadoxine/pyrimethamine, paracetamol and acetyl-
salicylic acid) available as tablet formulations on the
Tanzanian market.
Materials and methods
Samples
Table 1a–d shows the detailed information on the tablet
formulations that were evaluated for quality. The drugs
were selected on the basis of being included in the
Tanzanian national essential drugs list and common
usage. The drugs were sampled in Dar es Salaam from
two sources: the Tanzanian Medical Stores Department
(MSD) and 10 registered pharmaceutical wholesalers. The
MSD is an autonomous body that imports and distributes
drugs to all Government health facilities in the country.
The pharmaceutical wholesalers are among the major
importers and were selected based on the pharmaceuti-
cals’ importation data obtained from the Pharmacy Board
(Tanzania). Both the MSD and the wholesalers are
multisource importers of pharmaceuticals. The drugs
were anonymously purchased in their original package as
supplied by the manufacturers, and only one package of a
particular brand was bought from one wholesaler.
Samples from the MSD (one chloroquine and two
paracetamol formulations) were donated to the resear-
chers. All formulations sampled had a remaining shelf life
of at least 2 years at the time of sampling. The reference
formulations for acetylsalicylic acid, chloroquine and
paracetamol tablets were purchased from a pharmacy in
Belgium.
Drug standards
Acetylsalicylic acid, phenacetin and pyrimethamine were
obtained from Sigma Aldrich (Steinheim, Germany).
Chloroquine phosphate was obtained from Alpha Pharma
(Zwevegem, Belgium). Paracetamol was obtained from
Mallinckrodt Chemical (Raleigh, NC, USA), while salicylic
acid was obtained from Ludeco (Brussel, Belgium).
Sulphadoxine was purchased from Indis (Aartselaar,
Belgium).
Reagents
All reagents used during drug assay were of high-pressure
liquid chromatography (HPLC) grade, the other reagents
were of analytical grade. Formic acid and 1-heptane
sulphonic acid were obtained from Sigma Aldrich.
Monobasic potassium phosphate and glacial acetic acid
were obtained from Merck (Darmstadt, Germany).
Hydrochloric acid, monobasic sodium phosphate, tribasic
sodium phosphate, sodium hydroxide and orthophos-
phoric acid were purchased from Vel (Leuven, Belgium).
Methanol and acetonitrile were purchased from Biosolve
(Valkenswaard, the Netherlands), while perchloric acid
was obtained from UCB (Leuven, Belgium).
In vitro analysis
Assays
All drugs were assayed for the drug content immediately
after purchase. The tested tablets were randomly selected
from different packages of the same batch. The assays were
repeated three times and the results presented are the mean
of three determinations.
With the exception of chloroquine, all drugs were
assayed according to methods outlined in the individual
drug monographs of the United States Pharmacopoeia
(USP) 24 (USP 2000). Chloroquine tablets were assayed by
the technique described by Pussard et al. (1986). In all
assays particular emphasis was put on linearity of the
calibration curve over the expected working range and on
the accuracy and precision of the method. The relative
standard deviation (RSD) for repeated injection of the
standard samples was determined within-day and between-
days.
Drug dissolution and stability test
The stability of the in vitro availability of each formula-
tion under tropical conditions was investigated by per-
forming an accelerated stability test under zone IV climatic
conditions as recommended for Tanzania by the Interna-
tional Convention on Harmonization (Grimm 1998). The
samples were put in a sealed chamber containing a
saturated sodium chloride solution (RH 75 ± 5%) and
stored in an oven (Memmert, Namen, Belgium) main-
tained at 40 ± 2 °C. The dissolution profiles of each drug
were determined immediately after purchase and after 3
and 6 months storage at the above-mentioned conditions.
The dissolution methods described in the USP 24 were
used.
Tropical Medicine and International Health volume 7 no 8 pp 701–707 august 2002
P. G. Risha et al. In vitro evaluation of essential drugs
702 ª 2002 Blackwell Science Ltd

3. Equipment
The HPLC assays were carried out using a L-7110
isocratic pump, an L-7400 UV/VIS detector and a L-7000
integrator (Merck). The column used for each drug was as
prescribed in the respective USP monograph. For the
analysis of chloroquine tablets, a LiChrospherÒ
100RP
C18 end capped column (10 lm, 39 mm · 25 cm)
(Merck) was used. A VanKel VK 7010 dissolution
apparatus coupled with a VK 8000 automatic sampler
(VanKel Technology, Cary, NC, USA) was used for the
dissolution tests. A Lambda 12 UV/VIS Spectrophotometer
(Perkin Elmer, Norwalk, CA, USA) was used to determine
the concentration of paracetamol, chloroquine and
acetylsalicylic acid in the dissolution media. Analysis of
the sulphadoxine/pyrimethamine samples required HPLC
separation combined with UV determination as described
in the USP 24.
Results
Acetylsalicylic acid tablets
The RSD for replicate injections was 0.75 and 1.25% for
within-day and between-days analysis, respectively. The
Table 1 (a) Acetylsalicylic acid 300 mg tablet formulations. (b) Sulphadoxine (500 mg)/pyrimethamine (25 mg) tablet formulations.
(c) Chloroquine phosphate 250 mg tablet formulations. (d) Paracetamol 500 mg tablet formulations
Manufacturer Package Batch number
Price per 1000s
units (US$)
(a)
Bayer* (Belgium) Blister, 100 tablets 98 A05 37.5
Shelys Pharmaceutical Industries (Tanzania) Bulk, 1000 tablets 5497 1.3
Betahealth (Kenya) Bulk, 1000 tablets 1700 1.3
Mansoor Daya Chemicals (Tanzania) Bulk, 1000 tablets 214372 1.3
(b)
Rocheà, Switzerland Blister, 250 tablets B3015 350.0
Ellys Chemical Industries (Kenya) Blister, 100 tablets OE84 120.0
Shelys Pharmaceutical Industries (Tanzania) Blister, 100 tablets 068 120.0
Flamingo Pharmaceuticals (India) Blister, 100 tablets 5560 130.0
(c)
Rhoˆne Poulenc Rorer§ (Belgium) Bulk, 100 tablets 96J17 N/A
Shanghai Simplex (China) Bulk, 1000 tablets F610080 8.3
Shelys Pharmaceutical Industries (Tanzania) Bulk, 1000 tablets 573 Free sample
TPI (Tanzania) Bulk, 1000 tablets LK 72 8.3
Mepro Pharmaceuticals– (India) Bulk, 1000 tablets 9048 8.5
ACE labs (India) Bulk, 1000 tablets T70120 8.5
Taiyuan Yangling Shanxi (China) Bulk, 1000 tablets 971001 8.8
(d)
Jansen–Cilagà (Belgium) Blister, 100 tablets 99GO5B110 N/A
Medopharm (India) Bulk, 1000 tablets M6018 Free sample
Medopharm (India) Bulk, 1000 tablets M0173 3.2
TPI (Tanzania) Bulk, 1000 tablets LK 72 Free sample
TPI (Tanzania) Bulk, 1000 tablets NH 231 3.0
AlferezPVT (India) Bulk, 1000 tablets CTC )378 3.0
Interchem Pharma (Tanzania) Bulk, 1000 tablets 951203 3.0
Panacea Biotec (India) Blister, 100 tablets 101569 5.0
Granules (India) Blister, 100 tablets 084 5.0
FDC (India) Bulk, 1000 tablets F-103 3.0
* Reference formulation, contained 500 mg acetylsalicylic acid per tablet.
Market price if purchased in Dar es Salaam.
à Reference formulation.
§ Reference formulation, contained 100 mg chloroquine sulphate per tablet.
– Chloroquine phosphate sugarcoated tablets.
N/A: Not available on the Tanzanian market.
Tropical Medicine and International Health volume 7 no 8 pp 701–707 august 2002
P. G. Risha et al. In vitro evaluation of essential drugs
ª 2002 Blackwell Science Ltd 703

4. acetylsalicylic acid content in the samples ranged from
95.9 to 105.4%. This is within the acceptance range of
90–110% prescribed by the USP 24. The content of
salicylic acid in all the formulations was well below the
USP 24 tolerance limit of 0.3%.
The percentage of drug released from the acetylsalicylic
acid formulations is shown in Table 1a. Only the innovator
formulation from Bayer met the USP 24 dissolution
specifications (minimum of 80% within 30 min) by releas-
ing 98% of the labelled claim in 30 min. The samples from
Mansoor Daya, Betahealth and Shelys released only 38.3,
33.1 and 24.7% of the drug content in the same time
interval. On storage under the accelerated stability test
conditions, all the formulations showed a lower drug release
profile. Even the drug release rate of the Bayer formulation
was decreased to 90% in 30 min after 6 months in stability
(Fig. 1). The formulation from Shelys failed to disintegrate
during the dissolution test after exposure to the stability test
conditions.
Sulphadoxine/pyrimethamine tablets
The RSD was 0.26 and 0.73% for within-day and 0.86
and 1.44% for between-days analysis for sulphadoxine
and pyrimethamine, respectively. The resolution factor
between sulphadoxine and phenacetin (internal standard)
was 2.5, while it was 2.1 between phenacetin and
pyrimethamine. The content of sulphadoxine in the
samples ranged from 95.5 to 101.1%, while that of
pyrimethamine was 94.9–99.7%. These values fall within
the USP 24 acceptance range of 90–110% for both drugs.
The percentage of drug released for sulphadoxine and
pyrimethamine within 30 min from the different tablets
is shown in Table 2b. Before the stability test, only two
formulations (Ellys and Roche) met the USP 24
requirements for dissolution, that is a release of more
than 60% for both sulphadoxine and pyrimethamine
within 30 min.
On undergoing the stability test, the Ellys formulation
showed a progressive decrease in the drug release profile.
The sulphadoxine release decreased to 96.1 and 84.2%
after 3 and 6 months in stability, respectively. The
respective release of pyrimethamine during this period was
72.0 and 60.8%. The progressive decrease in the amount
of drug released was also observed for the formulation
from Shelys. The drug release from the Roche formulation
did not change appreciably during the entire stability test
period. The sulphadoxine release after 3 and 6 months of
storage under stability test was 92.0 and 89.3%, respect-
ively. The respective release of pyrimethamine was 63.2
and 60.4%. The drug release from the Flamingo formula-
tion remained well below the USP 24 tolerance limits
during the storage duration.
Chloroquine tablets
The RSD was 2.4 and 3.1% for within-day and between-
days analysis, respectively. The content of chloroquine
phosphate in the samples ranged from 95.9 to 105.4%.
For the Rhoˆne Poulenc Rorer formulation the assayed
amount of chloroquine sulphate was converted into the
equivalent amount of chloroquine phosphate. The
assayed amount of chloroquine phosphate for all the
samples was within the USP 24 acceptance range of
93–107%.
The dissolution data of the formulations are shown in
Table 2c. The dissolution tests carried out before the
samples were subjected to the storage conditions show that
all formulations conformed to the USP 24 requirements by
releasing more than 75% of drug in 45 min.
After exposure to the stability test conditions for
6 months, the in vitro drug release of five of the seven
formulations tested remained stable, their drug release
remaining well above 80% of labelled potency. The
Rhoˆne Poulenc Rorer and TPI formulations failed the
dissolution test. After 3 months stability testing, the
formulation from Rhoˆne Poulenc Rorer released only
83.4% of drug, a value that decreased to 50.3% after
6 months of storage under the test conditions (Fig. 2). The
TPI formulation released 54.9% of the drug after
3 months. This value decreased further to 42.2% after
6 months as the formulation failed to disintegrate but was
transformed into a sticky mass.
Figure 1 Dissolution profile of acetylsalicylic acid tablets from
the Bayer formulation after 0 (¤), 3 (j) and 6 (m) months of
storage under simulated tropical conditions (75% RH; 40 °C).
Tropical Medicine and International Health volume 7 no 8 pp 701–707 august 2002
P. G. Risha et al. In vitro evaluation of essential drugs
704 ª 2002 Blackwell Science Ltd

5. Paracetamol tablets
The RSD was 0.2 and 1.9% for within-day and between-
days analysis, respectively. The content of paracetamol in
the samples ranged from 92.9 to 99.5%. This lies within
the USP 24 acceptance range of 90–110%.
The percentage of drug released from the different
formulations is shown in Table 2d. Only two formulations
failed the initial dissolution test (minimum of 80% released
within 30 min). A batch from Medopharm sampled in
1998 released only 20% of the drug within 30 min (tablets
failed to disintegrate). However, a different batch from the
same manufacturer sampled in October 2000 passed the
dissolution test by releasing 100% of the drug within
30 min (tablets disintegrated). The other sample that failed
was from Interchem Pharma, releasing only 78.1% of the
labelled claim within 30 min.
On exposure to the stability test conditions, two addi-
tional brands (TPI and Alferez) had an unsatisfactory
in vitro drug release. The drug release of both batches from
TPI had already decreased to about 20% after 3 months of
stability testing. These tablets failed to disintegrate within
the 30 min of the testing period.
Discussion
We found price differences exist between different formu-
lations of the same drug on the Tanzanian market
(Table 1). In a free market situation this may be considered
normal and healthy, but the cost differential between the
innovator brand and generic equivalents is often large,
Table 2 (a) Percentage of drug released after 30 min of dissolu-
tion testing on acetylsalicylic acid tablets stored under simulated
tropical conditions (75% RH; 40 °C). USP 24 requirements: 80%
is released within 30 min. (b) Percentage of sulphadoxine and
pyrimethamine released after 30 min of dissolution testing on
sulphadoxine (500 mg)/pyrimethamine (25 mg) tablets stored
under simulated tropical conditions (75% RH; 40 °C). USP 24
requirements: more than 60% of both sulphadoxine and pyri-
methamine is released within 30 min. (c) Percentage of drug
released after 45 min of dissolution testing on chloroquine tablets
stored under simulated tropical conditions (75% RH; 40 °C). USP
24 requirements: more than 75% is released within 45 min.
(d) Percentage of paracetamol released after 30 min of dissolution
testing on paracetamol 500 mg tablets stored under simulated
tropical conditions (75% RH; 40 °C). USP 24 requirements: more
than 80% is released within 30 min
Storage time
Manufacturer 0 month 3 months 6 months
(a)
Bayer 98.1 94.3 90.2
Shelys 24.7 17.5 12.1
Betahealth 33.1 32.2 24.8
Mansoor Daya 38.3 37.2 36.8
(b)
Sulphadoxine
Roche 97.8 92.0 89.3
Ellys 100.2 96.1 84.2
Shelys 60.9 41.6 30.0
Flamingo 53.3 51.7 51.3
Pyrimethamine
Roche 66.4 63.2 60.4
Ellys 71.3 72.0 60.8
Shelys 26.5 20.0 13.6
Flamingo 17.4 17.2 15.6
(c)
Rhoˆne Polenc Rorer 96.0 83.4 50.3
Shanghai Simplex 96.3 95.1 89.8
Shelys 95.2 94.7 88.8
TPI 94.1 54.9 42.2
Mepro 95.3 92.5 85.1
ACE 90.8 89.9 89.5
Taiyuan Yangling 93.0 92.4 91.2
(d)
Jansen–Cilag 94.3 94.3 94.5
Medopharm (batch M6018) 20.0 19.2 18.0
Medopharm (batch M0173) 101.2 100.8 97.8
TPI (batch LK72) 88.8 21.5 20.0
TPI (batch NH231) 100.1 20.8 16.2
Alferez 92.0 56.3 50.0
Interchem 78.1 78.3 76.8
Panacea Biotec 101.6 100.1 99.9
Granules India 100.7 92.9 88.3
FDC 95.8 93.0 90.0
Figure 2 Dissolution profiles of chloroquine tablets from the
Rhoˆne Poulenc Rorer formulation after 0 (¤), 3 (j) and 6 (m)
months of storage under accelerated stability test conditions
(75% RH; 40 °C).
Tropical Medicine and International Health volume 7 no 8 pp 701–707 august 2002
P. G. Risha et al. In vitro evaluation of essential drugs
ª 2002 Blackwell Science Ltd 705

6. being well in excess of 100%. In a country where
affordability is a problem, the market will be dominated by
the cheaper alternatives of the drug. In this case it is
important that the drug regulatory authority in Tanzania
put in place the necessary controls to ensure that drugs on
the market are consistently of good quality.
The assay results on the content of the active substance
showed that this parameter was for all formulations within
the specifications recommended by the USP 24. The
findings are similar to those obtained by Abdi et al. (1995)
on the quality of chloroquine tablets on market in
Tanzania, where all samples from 10 manufacturers passed
the assay test. However, Kibwage et al. (1992) reported
that about 45% of drugs sampled on the Kenyan market
and analysed at the Daru quality control laboratory on a
routine basis were of substandard quality in terms of the
content of the active ingredient. Shakoor et al. (1997)
reported both fake and substandard drugs on Thai and
Nigerian markets where 32% of 89 samples failed in the
assay determination. These differences in findings cannot
be explained on the basis of the existence of an effective
drug control and monitoring system in Tanzania. On the
contrary, such a system was not in place during the period
when the samples were taken. For example, it was only
until July 2000 when the Pharmacy Board of Tanzania
established the only drug control laboratory in the country,
and the drug registration exercise has taken place recently.
Although a major prerequisite, the effectiveness of an
oral solid dosage form is not entirely dependent on the
presence of the correct drug amount. The drug formulation
should be capable of releasing the drug into solution;
otherwise the drug may be presented at an unfavourable
absorption site or in the extreme case pass through the
gastrointestinal tract unabsorbed. So far the dissolution
test is the only in vitro quality control test that can
determine the capability of a formulation to release the
drug into solution. We were able to discriminate poor
quality formulations amongst the samples that had passed
the assay tests: 29% (7/24) of the analysed formulations
failed the initial dissolution test – three generic acetyl-
salicylic acid, two sulphadoxine/pyrimethamine and two
paracetamol formulations. Of the 17 samples that passed
the initial dissolution test, 35% (5/17) ) three paracetamol
and two chloroquine formulations – failed the dissolution
test after undergoing a stability test under simulated
tropical conditions.
Several studies have reported on the stability of essential
drugs under real storage conditions in the tropics
(Hogerzeil et al. 1991; Ballereau et al. 1997; Nazerali
et al. 1998). All these studies have dwelt on the chemical
stability of the drug. It is known that under conditions of
high temperature and humidity the drug may undergo
polymorphic or crystal changes that may decrease its
inherent solubility. In addition, excipient – excipient and/
or excipient – drug interactions may occur under influence
of high temperature and humidity storage conditions and
reduce the dissolution rate of a formulation containing a
chemically stable drug (Saville 2001). We observed dra-
matic changes in the dissolution behaviour of some
formulations. The paracetamol and chloroquine formula-
tions that failed the stability test had a more than 40%
reduction in the amount of drug released after 3 and
6 months of stability testing.
It was not possible to identify the cause of the failure in
dissolution of the formulations, as the exact composition of
the formulations was not available. It is known that
interactions that may occur as a drug formulation stored at
high temperature and humidity conditions are complex and
formulation-dependent (Murthy & Sellassie 1993). The
formulations may have contained disintegrants such as
maize starch, which can lose its capacity to swell on ageing
or exposure to high humidity/temperature (Pandit et al.
1997).
Dissolution is an important quality control test that
assesses the in vitro availability of the drug from the
formulation and therefore the absorption potential of a
drug, especially if it contains poorly soluble drugs. Failure
of a drug formulation to meet the USP dissolution
specifications could be an indication of potential bioavail-
ability problems. The sulphadoxine/pyrimethamine com-
bination has recently replaced chloroquine as first line drug
for the treatment of uncomplicated malaria in Tanzania.
Both components of the drug are poorly soluble. Dissolu-
tion is expected to be the rate limiting step in their
absorption. Both the drugs have a weak anti-Plasmodium
activity, but when combined in a 20:1 ratio in favour of
sulphadoxine, this activity is augmented by a synergistic
action. Their effectiveness would depend on the bioavail-
ability of both components after oral administration. The
poor dissolution characteristics of some of the sulphadox-
ine/pyrimethamine samples thus casts doubt on their
effectiveness. The emerging drug resistance to antimalarial
drugs has been associated with suboptimal drug regimens
or the use of substandard drugs (Petralanda 1995). To
prolong the effectiveness of this newly introduced treat-
ment regimen, it is prudent to withdraw the sulphadoxine/
pyrimethamine formulations failing the dissolution tests
from the market.
Conclusion
There are drug formulations on the Tanzanian market,
which although they satisfy potency specifications, fail to
meet dissolution requirements. Some formulations were
Tropical Medicine and International Health volume 7 no 8 pp 701–707 august 2002
P. G. Risha et al. In vitro evaluation of essential drugs
706 ª 2002 Blackwell Science Ltd

7. not robust enough to withstand tropical climatic condi-
tions during storage and distribution. The regulatory
authorities need to develop a quality assurance system to
ensure that such drugs are withdrawn.
Acknowledgements
P. G. Risha holds a PhD scholarship from the Belgian
Technical Co-operation (BTC). BTC also granted Masters
scholarships to D. Shewiyo, A. Msami and G. Masuki. We
thank the Muhimbili University College of Health Sciences
(MUCHS) Tanzania for funding the purchase of the
samples.
References
Abdi YA, Rimoy G, Ericsson O, Alm C & Massele AY (1995)
Quality of chloroquine preparations marketed in Dar es Salaam,
Tanzania. Lancet 346, 1161.
Ballereau F, Prazuck I, Schrive M et al. (1997) Stability of essential
drugs in the field: results of a study conducted over a two year
period in Burkina Faso. American Journal of Tropical Medicine
and Hygiene 57, 31–36.
Gilson L, Jaffar S, Mwankusye S & Teuscher T (1993) Assessing
prescribing practice: a Tanzanian example. International Jour-
nal of Health Planning and Management 8, 37–58.
Grimm W (1998) Extension of the International Conference on
Harmonisation: tripartite guidelines for stability testing of new
drug substances and products to countries of climatic zones III
and IV. Drug Development and Industrial Pharmacy 24,
313–325.
Hogerzeil HV, De Goeje MJ & Abu-Reid IO (1991) Stability of
essential drugs in Sudan. Lancet 338, 754.
Kibwage IO, Ogeto JO, Maitai CK, Rutere G, Thuranira J &
Ochieng A (1992) The quality work in Daru: observations
during 1983–86. East African Medical Journal 69, 577–580.
Massele AY & Mwaluko GP (1993) A study of prescribing pat-
terns at different health facilities in Dar es Salaam Tanzania.
East African Medical Journal 71, 314–316.
Murthy KS & Ghebre-Sellassie I (1993) Current perspectives on
the dissolution stability of solid oral dosage forms. Journal of
Pharmaceutical Sciences 82, 113–126.
Nazerali H, Muchemwa T & Hogerzeil HV (1998) The quality
and stability of essential drugs in rural Zimbabwe: controlled
longitudinal study. British Medical Journal 317, 512–513.
Pandit JK, Tripathi MK & Babu RJ (1997) Effects of disintegrants
on the dissolution stability of solid oral dosage forms. Phar-
mazie 52, 538–540.
Petralanda I (1995) Quality of antimalaria drugs and resistance to
Plasmodium vivax in Amazonian Region. Lancet 345, 1433.
Pussard E, Verdier F & Blayo MC (1986) Simultaneous determin-
ation of chloroquine, amodiaquine and their metabolites in
human plasma, red blood cells and urine by column liquid
chromatography. Journal of Chromatography 374, 111–118.
Saville DJ (2001) Influence of storage on in-vitro release of ibu-
profen from sugar coated tablets. International Journal of
Pharmaceutics 224, 39–49.
Shakoor O, Taylor RB & Behrens RH (1997) Assessment of the
incidence of substandard drugs in developing countries. Tropical
Medicine and International Health 2, 839–845.
Taylor RB, Shakoor O, Behrens RH et al. (2001) Pharmacopoeial
quality of drugs supplied by Nigerian pharmacies. Lancet 357,
1933–1936.
United States Pharmacopoeia Convention INC (2000) The United
States Pharmacopoeia 24 Nf19. INC, Rockville.
World Health Organization (1988) The World Drug Situation.
WHO, Geneva.
Tropical Medicine and International Health volume 7 no 8 pp 701–707 august 2002
P. G. Risha et al. In vitro evaluation of essential drugs
ª 2002 Blackwell Science Ltd 707