Evaluation and characterisation of bioadhesive suppositories formulated using commercial hydrogenated palm kernel stearin

Lau, Hui Ling (2016) Evaluation and characterisation of bioadhesive suppositories formulated using commercial hydrogenated palm kernel stearin. PhD thesis, University of Nottingham.

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Rectal route of drug administration is particularly useful when patients cannot tolerate orally yet are unable to receive parenteral injections. Furthermore, studies have shown that it may be possible to circumvent first pass metabolism if absorption was localised in lower rectum. This is theoretically achievable if suppositories were bioadhesive.

The aim of this thesis was to evaluate two types of commercial hydrogenated palm kernel stearin (HPKS) namely ChocExa (CE) and Supersocolate SpecialTM (SS) as base candidates for bioadhesive suppositories in comparison to cocoa butter (CB). Robustness of these bases during suppository manufacturing was compared using both DSC-simulated and extemporaneous methods. Diclofenac sodium (DcNa) which undergoes extensive first pass metabolism was selected as model drug. Suppositories containing 50 mg DcNa and 1-5 %w/w bioadhesive polymers manufactured using CB, CE and SS as base were evaluated in terms of physical properties, drug release, bioadhesive properties as well as stability under different storage conditions. The bioadhesive polymers used were Carbopol® 974P NF (CBP), hydroxypropyl methylcellulose 2910 (HPMC), poly(vinylpyrrolidone) K30 (PVP) and carboxymethyl chitosan (CMCTS). Two self-fabricated methods using the texture analyser (tensile and shear stress) were developed to study bioadhesion of suppositories against porcine colon mucosa under simulated rectal conditions.

Physical characterisation found that CE and SS were comparable to CB in terms of thermal profile, solid fat content (SFC), pH, viscosity and displacement values (DV) but with added advantages of reduced polymorphism and less stringent manufacturing parameters. Solidification of CB melt into suppositories was highly dependent on the maximum heating temperature (Tmax) and cooling rate (Crate). HPKS on the other hand were more robust, as long as it is completely molten HPKS would solidify into stable β’ polymorph; while cooling rates did not affect crystallisation. All the bioadhesive suppositories melt between 32.5-35.5 °C. Addition of CBP decreased rate and extent of DcNa release in a concentration dependent manner, resulting in bi-exponential first-order kinetics release pattern. The other bioadhesive polymers had minimal impact on DcNa release. The tensile method to study bioadhesion found that bioadhesive properties decreased in the order of PVP > CBP > CMCTS > HPMC while the shear method PVP > CMCTS > CBP = HPMC. In both instances, HPMC showed poor bioadhesion with limited benefit in development of bioadhesive suppositories. Formulations containing 5 %w/w PVP and CMCTS were selected for subsequent stability assessment based on considerations of complete DcNa release and good bioadhesive properties. These suppositories required refrigeration as suppositories stored for 200 days at room temperature (24.5 ± 2.5 °C; RH 58 ± 5 %) showed graininess and loss of surface glossiness, increased melting point, possible triacylglycerol (TAG) separation, higher SFC at 37 °C, prolonged softening times and decreased amount of DcNa release. These changes were unfavourable for suppositories and may lead to ineffective treatment. Generally, SS suppositories subjected to accelerated ageing released DcNa more efficiently than CE.

Although both HPKS were suitable suppository base substitutes of CB, SS provided superior stability in terms of resistance to depression of DcNa release. PVP on the other hand conferred the best bioadhesive properties among all polymers evaluated. Thus, SS suppositories incorporated with 50 mg DNa and 5 %w/w PVP may be a potential candidate for further development.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Tung, Wai Hau
Keywords: suppositories, bioadhesive, hydrogenated palm kernel stearin, Carbopol® 974P NF, hydroxypropyl methylcellulose 2910, poly(vinylpyrrolidone) K30, carboxymethyl chitosan
Subjects: R Medicine > RS Pharmacy and materia medica
Faculties/Schools: UNMC Malaysia Campus > Faculty of Science > School of Pharmacy
Item ID: 29683
Depositing User: LAU, HUI LING
Date Deposited: 13 Dec 2017 10:05
Last Modified: 21 Dec 2017 01:24
URI: http://eprints.nottingham.ac.uk/id/eprint/29683

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