The Role of Functional Excipients in Solid Oral Dosage Forms to Overcome Poor Drug Dissolution and Bioavailability

Many active pharmaceutical ingredients (APIs) exhibit poor solubility and low dissolution rates in aqueous environments such as the luminal fluids of the gastrointestinal tract. The oral bioavailability of these compounds is usually very low as a result of their poor solubility properties. In order to improve the bioavailability of these poorly soluble drugs, formulation strategies have been applied as a means to improve their aqueous solubility and dissolution rates. With respect to formulation approaches, excipients can be incorporated in the formulation to assist in the dissolution process of the drug, or specialized dosage forms can be formulated that improve dissolution rate through various mechanisms.

This paper provides an overview of selected excipients (e.g., alkalinizing agents, surfactants and sugars) that can be used in formulations to increase the dissolution rate as well as specialized dosage forms such as self-emulsifying delivery systems and formulation techniques such as inclusion complexes and solid dispersions. These formulation approaches are discussed with available examples with specific reference to positive outcomes in terms of drug solubility and bioavailability enhancement.

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van der Merwe, J.; Steenekamp, J.; Steyn, D.; Hamman, J. The Role of Functional Excipients in Solid Oral Dosage Forms to Overcome Poor Drug Dissolution and Bioavailability. Pharmaceutics 2020, 12, 393.

 

SEE ALSO THE OVERVIEW OF EXCIPIENTS ROLES IN OUR BASIC ARTICLE

Summary of functional excipients used in different types of dosage forms to improve drug solubility and dissolution rate.

Excipient Type	Excipient Subdivision	Drug Example	In Vitro/In Vivo	Dosage Form Type
Cyclodextrin	β-Cyclodextrin	Eslicarbazepine	in vitro + in vivo	Orodispersable tablet (solid dispersion)
Cyclodextrin	HP(2-Hydroxypropyl)-β-Cyclodextrin	Carbamazepine, Naproxen	in vitro + in vivo	Immediate release tablet/ Enteric coated tablet
Disintegrants	Croscarmellose Sodium and Jackfruit starch	Irbesartan	in vitro + in vivo	Direct compressed fast disintegrating tablet
Disintegrants	Sodium starch glycolate and crospovidone	Valsartan	in vitro + in vivo	Direct compressed fast disintegrating tablet
pH adjusting excipients	Citric acid	Ketoconazole	in vitro + in vivo	Physical mixture (granules)
pH adjusting excipients	Tartaric acid	Ketoconazole	in vitro + in vivo	Physical mixture (granules)
pH adjusting excipients	Sodium Hydrogen Carbonate	Paracetamol	in vitro + in vivo	Controlled release matrix tablet
pH adjusting excipients	Calcium Carbonate	Paracetamol	in vitro + in vivo	Controlled release matrix tablet
pH adjusting excipients	di-Sodium Carbonate	Aceclofenac	in vitro + in vivo	Controlled release matrix tablet
pH adjusting excipients	di-Sodium Carbonate	Aceclofenac	in vitro + in vivo	Nanoemulsifying GUC (Gelucire 44/14)-based solid dispersions
Solid dispersions	Tocopherol polyethyleneglycol-1000-succinate	Dutasteride	in vitro + in vivo	Physical mixture (solid dispersion)
Solid dispersions	Polyethylene glycol, polyvinyl acetate and polyvinylcaprolactame-based graft co-polymer	Nilotinib	in vitro	Encapsulated physical mixture (spray-dried mixture)
Solid dispersions	Hydroxypropyl methylcellulose acetate succinate	Posaconazole	in vitro + in vivo	Delayed release tablet
Solid dispersions	Chitosan	Curcumin	in vitro + in vivo	Amorphous solid dispersion
Surfactant	Sodium lauryl sulphate	Celecoxib, Tramadol, Methocarbamol, Diazepam, Alprazolam, Buspirone, Gabapentin and Acetaminophen	in vitro	Direct compressed tablet
Surfactant	Tween 20, Tween 40, Tween 60, Tween 80, sodium dodecyl sulphate and	Ibuprofen	in vitro	Oral solution
Surfactant	D-α-tocopherol polyethylene glycol 1000 succinate	Paclitaxel	in vitro + in vivo	Oral mixture
Surfactant	D-α-tocopherol polyethylene glycol 1000 succinate	Dutasteride	in vitro + in vivo	Physical mixture (solid dispersion)
SNEDDS	Capryol-90, Tween 80 and PEG-400	Nabumetone	in vitro + in vivo	Oral SNEDDS
SMEDDS	capryol 90, lauroglycol 90, carbitol, PEG 400, polypropylene glycol and cremophor EL	Simvastatin	in vitro + in vivo	Oral SMEDDS
Mucoadhesive/Mucopenetrating polymer	Chitosan	Telmisartan	in vitro + in vivo	Oral co-crystals
Mucoadhesive/Mucopenetrating polymer	Chitosan	Carvedilol	in vitro + in vivo	Oral nanoparticles
Sugars	Sucrose laurate	Gemfibrozil	in vitro	Oral solid dispersion
Sugars	Mannitol	Ketoprofen	in vitro + in vivo	Oral co-crystals
Sugars	Mannitol	Meloxicam	in vitro + in vivo	Oral co-crystals
Soluble and insoluble fillers	MCC	Quercetin	in vitro + in vivo	Oral co-crystals
Soluble and insoluble fillers	Lactose	Bicalutamide	in vitro	Oral nanodispersion

Table as per: van der Merwe, J.; Steenekamp, J.; Steyn, D.; Hamman, J. The Role of Functional Excipients in Solid Oral Dosage Forms to Overcome Poor Drug Dissolution and Bioavailability. Pharmaceutics 2020, 12, 393.