Inserts, implants, and devices represent pharmaceutical interventions in healthy and/or disease states that may be used to improve health and/or promote quality of life.
Inserts, as the name implies, are drug delivery systems that are designed for insertion into one or the other body cavity, such as vagina, rectum, buccal cavity, or the cul-de-sac of the eye, in the patient.
Suppositories are solid dosage forms that are used to administer drugs through the rectum or vagina.
Implants, on the other hand, are designed for surgical placement inside the body, such as in the subcutaneous (SC) tissue, breast, penis, heart, bones, teeth, eye, or the ear.
Devices are recognized as relatively sophisticated drug delivery systems intended for a specific application, such as transdermal drug delivery, intrauterine devices (IUDs), ventricular assist devices, and insulin pumps and pens. Transdermal patches are used for drug delivery across the skin. Aerosols and inhalation drug delivery devices are used for pulmonary drug delivery.
Inserts, implants, and devices may or may not be loaded with drug(s). Drug containing inserts, implants, and devices are used to deliver drugs for localized or systemic effects. Sometimes, the rate of drug release is controlled. In such cases, the drug may embed into biodegradable or non-biodegradable materials forming a uniform matrix that allows slow release of the drug.
Drug administration to the eye commonly involves the use of eye drops, which can be formulated as a drug solution or suspension, or as semi-solid ointments. Tear turnover and drainage can quickly eliminate the administered drug, reducing the amount of drug absorbed into the eye. Less than 10% of a topically applied dose is usually absorbed into the eye. A part of the dose also passes into the nasal sinus and is absorbed through the highly vascular nasal mucosa into the bloodstream. This may result in unwanted systemic side effects.
For example, topical administration of latanoprost (Xalatan®) eye drops, a prostaglandin PGF2α analogue used to treat glaucoma, can result in chest tightness in some patients. Similarly, the use of topical α-blockers, such as timolol, for glaucoma treatment can lead to systemic side effects, such as hypotension and bradycardia. These safety concerns are addressed by the use of inserts that stay on the cornea for long duration of time.
Inserts can be biodegradable or nonbiodegradable. Inserts can also be designed for immediate or controlled drug release. Drug containing inserts are placed on the cornea, sometimes hidden below the eyelid, by the patient. These inserts are designed to maintain drug concentration in the precorneal fluids at relatively steady levels over a prolonged period of time and allow drug diffusion across the cornea. Ocular inserts are less affected by nasolacrimal drainage and tear flow than conventional dosage forms. They can provide slow drug release and longer residence times in the conjunctival cul-de-sac.
Ocular inserts (e.g., medicated contact lenses, collagen shields, and minidiscs) also reduce systemic absorption of topically applied drugs as a result of decreased drainage into the nasal cavity. In addition, contact lenses are becoming increasingly useful as potential drug delivery devices by presoaking them in drug solutions. The use of contact lenses can simultaneously correct vision and release drug.
The ophthalmic inserts can be insoluble or soluble. Insoluble inserts may or may not be erodible/biodegradable. Insoluble inserts are further classified as diffusional, osmotic, and contact lens. Biodegradable inserts consist of degradable polymers such as polyvinyl alcohol (PVA), hydroxypropylcellulose (HPC), polyvinylpyrrolidone (PVP), and hyaluronic acid.
Nonbiodegradable inserts are prepared from insoluble materials such as ethylene–vinyl acetate copolymers and styrene–isoprene–styrene block copolymers.
A suppository is a solid dosage form designed for easy insertion into body orifices of rectum, vagina, or urethra. Once inserted, the suppository base melts, softens, or gets dissolved at body temperature, distributing its medication to the tissues of the region. Suppositories are used for local or systemic effects. Suppositories are also used to administer drugs to infants and small children, to severely debilitated patients, to geriatric patients who cannot take medications orally, and to those for whom both the oral and the parenteral routes may not be suitable. Vaginal or rectal suppositories are sometimes also termed as pharmaceutical pessaries (singular, pessary).
Based on their route of administration, suppositories can be rectal, vaginal, or urethral.
• Rectal suppositories are cylindrical or conical in shape. Suppositories containing a moisturizer or a vasoconstrictor are often used to relieve the pain, irritation, itching, and inflammation associated with hemorrhoids. Glycerin or bisacodyl suppositories are used as a laxative. They may also be used for systemic administration of drugs, such as opiate analgesics. Rectal suppositories are often intended for systemic drug action. Examples of such rectal suppositories include Thorazine® (chlorpromazine) and Phenergan® (promethazine HCl).
The suppository dissolves at body temperature and gradually spreads over the lining of the lower bowel (rectum), from where it is absorbed into the bloodstream. The medicine is easily absorbed from the rectum, because there is a rich supply of blood vessels in this area. Addition of surfactants may increase the wetting and spreading of the molten mass, which tends to increase the extent of drug absorption. Surfactants, such as polyoxyethylene sorbitan monostearate and sodium lauryl sulfate, may also increase the permeability of the rectal mucosal membrane resulting in significant increase in drug absorption.
• Vaginal suppositories are available in ovoid, globular, or other shapes. They are employed as contraceptives, antiseptics in feminine hygiene, treatment of local vaginal infections (e.g., candidiasis), or for systemic delivery of hormones (e.g., progesterone), with high local concentration, especially in the uterus.
• Urethral suppositories are sometimes used for the treatment of severe erectile dysfunction. For example, alprostadil pellets that contain the vasodilator prostaglandin E1 is marketed under the trade name MUSE® (medicated urethral suppository for erection).
Vaginal rings, also known as V-rings or intra-vaginal rings, are doughnut shaped polymeric drug delivery devices designed to provide controlled release of drugs to the vagina. They are manually placed in vagina and are held in place by the anatomy, usually close to the cervix.
• Nuvaring® is a contraceptive vaginal ring that contains etonorgestrel (progestogen) and ethinyl estradiol (estrogen). It is made using poly (ethylene-co-vinyl acetate) polymer and provides slow release of hormones over a period of 3 weeks.
• Estring® is a low-dose estradiol-releasing ring for treating vaginal atrophy.
• Femring® is a low-dose estradiol acetate-containing ring. It is used for vaginal atrophy and hot flashes. It can provide drug release over a period of 3 months.