PRESCRIPTION ANALYSIS FOR EXTEMPORANEOUS PREPARATIONS IN HOSPITAL PHARMACIES OF SOUTHERN NIGERIA

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STATEMENT OF THE PROBLEM
Today extemporaneous preparations find greater use in community and hospital pharmacies worldwide, including Nigeria.This is chiefly due to reconstitution/tailoring of medications to individual patients needs either by reason of "per body weight" dosing system, difficulty in swallowing, frailty in organs of metabolism or unavailability of required dosage forms.In Nigeria most (>95 %) of the extemporaneously prepared medications are oral dosage forms.

ANALYSIS OF RECENT RESEARCH
AND PUBLICATIONS In Nigeria, USA, Australia, Malaysia and some European countries, it is a common practice for these medications to be prepared from a commercially available oral solid dosage form by crushing tablets or mixing contents with a dispersion medium (base/vehicle) [2,9,[12][13][14][15][16]. According to the British Pharmaceutical Codex, medicated and flavouring syrups provide a convenient form of stock solution of certain drugs for use in extemporaneous preparations [3].

IDENTIFICATION OF ASPECTS OF THE PROBLEM UNSOLVED PREVIOUSLY
While other nations have progressed with finding solutions to this not so recent development, stakeholders in Nigeria are yet to give the much needed attention.For stability studies to be undertaken for compounded preparations, one must sort out the local needs of the region in terms of frequently prescribed medications, cost and availability of components of extemporaneous preparations etc. © Alfred-Ugbenbo D. S., Zdoryk O. A., Georgiyants V. A., 2016

OBjECTIVE STATEMENT OF THE ARTICLE
The aim of the work was to analyse frequently compounded prescriptions in south-south geopolitical region of Nigeria, stability study concerns of compounded preparations and bases/vehicles used in compounding.

PRESENTATION OF THE MAIN MATERIAL OF THE RESEARCH
The study was conducted using prescriptions obtained from the University of Port-Harcourt Teaching Hospital, Rivers State (UPTH) and another major hospital in the southern part of Nigeria, which preferred to remain anonymous (XGH).A combination of closed and open-ended format questionnaire, distributed to pharmacists in the UPTH, was used to obtain information on APIs and vehicles/ bases used in compounding and its cost.Data from both prescriptions and questionnaire were analysed into Microsoft Excel 2010 and summarized in tables.
A total of 1157 relevant prescriptions from the period of January 2014 -September 2015 were assessed for the study.Hospital XGH allowed access to information on compounded prescriptions under the conditions of anonymity but did not give permission to conduct a questionnaire survey.A total of 42 out of 43 questionnaires distributed to compounding pharmacists were returned, representing a 97.7 % response rate of the sample size.Mean scores were determined for each item and the summarized data presented below.
From Fig., ciprofloxacin and spironolactone are the most frequently compounded prescriptions for XGH and UPTH respectively.These drugs are indicative of infectious diseases and ailments associated with the cardiovascular system.Other frequently compounded drugs include digoxin, hydro- At XGH (Tab.2), the most recurring duration (regime) for which the compounded drugs were prescribed was one week while the maximum duration was two weeks.In UPTH (Tab.3), the most recurring duration was also one week while the maximum duration was for one month.
It was observed that most of the extemporaneous preparations in UPTH are made using APIs from commercial drugs.Although imported bases/ vehicles (ORA-Plus, ORA-Sweet etc.) are used, pharmacists admit to have used (one time or the other in their years of practice) locally available medicated syrups (LAMS) as dispersion medium for prescribed active components.Compounding in Nigeria is done majorly in hospital pharmacies.This writer and majority of pharmacists are not aware of any stability tests on extemporaneous formulations conducted in/for the country.
Stability concerns.Hitherto, there hasn't been a stability study of extemporaneous preparations made from these medicated syrups in Nigeria.Syrups of ascorbic acid and Vitamin B Complex have been occasionally (frequently in some cases) used [1] although stability tests haven't been conducted or made available.Some internationally published stability tests have been conducted using APIs from specific commercial drugs [4,7,15,16].However, one cannot guarantee that all compounding pharmacists (worldwide) make use of those APIs from specific pharmaceutical firms with which stability test was conducted.Rather, there is a greater possibility that APIs of commercial drugs used by most compounding pharmacists may be different from those used in successfully carried out and published stability data.
Secondly, different pharmaceutical firms use different excipients in producing one and the same class of drugs [6].Absence of a standard recipe and APIs (of commercial fixed-dose drugs) of specific pharmaceutical firms paves the way for use of different APIs and dispersion media of which different excipients may constitute.This produces different risks in stability [8,19] and consequently, increase uncertainty in allocated beyond-use-dates (BUDs).
The APIs generally used for compounding in hospital pharmacies in Nigeria are commercially available fixed-dose drugs (tablets, capsules, injections etc).Pure substances (as APIs) for compounding are rarely purchased.All drugs, extemporaneously prepared in the hospitals were packaged in well closed amber bottles to prevent photolabile degradation [9].Patients were advised to store at recommended temperatures and away from children's reach.Suspensions were labelled "shake well before use".
Prospective substitutes.Not all hospital pharmacies in the country use imported vehicles (IMPVs) such as ORA-Sweet, ORA-Sweet SF, ORA-Plus, Cherry syrup etc. in compounding.During shortage of supply, patients won't be turned away [5]; hospital pharmacies may have to improvise by using alternative vehicles for dispersing prescribed APIs.This leaves the option of locally readily available syrups (LAMSs) such as medicated syrups of ascorbic and Vitamin B complex.It is imperative that such tests be carried out for these syrups since they have occasionally been used.The results of these tests will provide assured BUDs.The problem of For a population with 30 % below the poverty line of $1.25 power purchasing parity (PPP) [20], affordability of drugs is a significant factor in total therapeutic outcome.
At XGH, the most frequent duration (regime) for which the compounded drugs were prescribed was one week while the maximum duration was two weeks.In UPTH, the most frequent duration is also one week while the maximum duration was one month.If these LAMSs could maintain the integrity of the APIs for a month, they will serve as a readily available substitute.In a situation where the APIs are stable for two weeks or 10 days, the patients could be asked to come for a refill when the conservative BUD approaches.
Most of the prescriptions have an average duration of seven to ten days (Tab.2).This is to help physicians assess response to treatment or reduction of disease indicators.Also, it encourages adherence/compliance to treatment, which becomes difficult when prescription is for a long duration [18].Nigerian parents are not comfortable either taking their children for prolonged visits or leaving their children in hospitals beyond two weeks.Oftentimes alternative solutions to health problems are sought after [7,10,17].They include spiritual (prayers and prayer houses), local massage therapists, proven and unproven herbal (non-orthodox) formulations sold by vendors.
Based on the average duration in table 2 and 3, initial/low-cost stability tests could be conducted for up to 40 days maximum, for which BUDs could be established.

CONCLUSIONS AND PROSPECTS
FOR FURTHER RESEARCH Based on the analysis of frequently compounded prescriptions, ciprofloxacin, spironolactone, digoxin, hydrochlorothiazide, acetazolamide, furosemide and captopril constitute majority of extemporaneous medications prepared in these hospitals.The APIs used for compounding in hospital pharmacies in southern Nigeria are commercially available fixeddose drugs (tablets, capsules and injections).
Oral dosage forms make up more than 99 % of extemporaneous prescriptions analysed in these hospitals.Imported vehicles/bases such as ORA-Sweet, ORA-Sweet SF, ORA-Plus and Cherry syrup, used as the dispersion media, are more expensive than the proposed cheaper locally available medicated syrups.In order to reduce cost of these extemporaneously prepared medications the vehicles/bases have to be replaced by cheaper locally available medicated syrups.
Where successful stability studies have been conducted using APIs of commercially available drugs (of specific pharmaceutical firms), such APIs should be preferably used in formulation of compounded preparations; as APIs of different firms may be constituted of different excipients which may not produce the same shelf-life.The same applies when and if proposed medicated syrups pass stability tests.It is pertinent that government, hospital and all stakeholders in the Nigeria pay more attention to funding for stability tests and full equipment of compounding laboratories. [52]