INTRODUCTION:

Suppositories are solid dosage forms designed to be inserted into body orifices (such as the urethra, vagina, and rectal cavity), where they can exert a local or systemic effect after melting, softening, or dissolving.¹ The Latin term for "suppositories" means "to put under." Suppositories are for rectum, vagina, or urethra insertion and come in a variety of weights and forms. They are typically medicated. Suppositories soften, melt, disperse, or dissolve in the fluids of the cavity after being inserted.² Given that the medication is absorbed directly into the bloodstream through the rectal mucosa, it has a quicker beginning of action than the oral route.

(Avoids the first-pass metabolism). It is a practical approach to administer medications that make you throw up, irritate your GI system, or are ruined by the acidic pH of your stomach.³Pessaries and suppositories are effective single-dose medications used for rectal or vaginal administration. Suppositories (pessaries) should be the right size, shape, and consistency for rectal or vaginal administration.^4.5 The complicated interaction between medicinal ingredients and the suppository substrate, which offers structural-mechanical or rheologic qualities, determines the therapeutic impact of suppositories. One of the key factors affecting bound-dispersed systems' stability is this property. The following criteria should be met by suppository bases: ensure maximum contact between therapeutic substances and mucous membranes; be sufficiently viscous; be sufficiently solid at room temperature and melt at body temperature (or dissolve in body secretions); be non-irritating, chemically and pharmacologically indifferent; and not be destructive when subjected to external influences. (Light, moisture, oxygen, etc.).^6.7 Both the medical and pharmaceutical fields have experienced tremendous growth during the last century. Drug compositions are constantly improving, and new ideas are being produced on a daily basis. Even though the rectal method of administration is not well-liked by the general public, it offers advantages and value in the medical industry. Since ancient times, suppositories have been used to treat proctological disorders.⁸ Rectal suppositories designed for localized action are most frequently used to treat hemorrhoids and hemorrhoids-related pain, irritation, itching, and inflammation. (E.g. Antiasthmatic, antirheumatic & analgesic drugs). The bases that are typically used are a blend of polyethylene glycols with different molecular weights, cocoa butter, glycerinated gelatin, hydrogenated vegetable oils, and gelatin.^9.10

SUPPOSITORIES v/s ORAL DOSAGE FORM:

Suppositories have a better bioavailability and a quicker onset than oral dose forms. Suppositories can be used instead of oral medication in the following circumstances because of their distinct advantages:

· Vomiting and having trouble swallowing tablets or liquids

· Unable to swallow medication due to seizures and being unable to take oral medications

· Too soon experience abdominal breakdown

· Tastes too unpleasant to consume.

· Destroyed in the digestive system

TYPES OF SUPPOSITORIES¹¹

There are five varieties of suppositories, each with a different method of administration.

1. Rectal Suppositories

2. Vaginal Suppositories

3. Urethral Suppositories

4. Nasal Suppositories

5. Ear Suppositories

In addition to suppositories, there are 4 other types of dosage forms available.

1. Tablet Suppositories

2. Layered Suppositories

3. Coated Suppositories

4. Capsule Suppositories

DEVELOPING PROCESS OF SUPPOSITORIES:

Fusion moulding, compression moulding, and hands moulding are the three different ways that suppositories are prepared. Generally speaking, hands moulding is only employed in pharmacies and fusion procedures can be applied to all kinds of suppositories. With this technique, the suppository matrix is first melted, the drug is then dispersed or dissolved in the melted matrix, and finally the mixture is poured into the suppository mould. Once the mixture coagulates, the suppository is then withdrawn from the mould.^{72, 73, 75}

DELIVERY OF SUPPOSITORY:

If a suppository is hydrophilic or lipophilic, it will initially dissolve in the liquid or melt on the mucous layer. Water is pulled to the rectum or vagina as a result of the dissolving vehicle's osmotic effects, and when the suppository melts and dissolves, the medications it contains will diffuse out towards the mucosal epithelial surfaces.^{12, 74}

If the medication is water immiscible, it must first escape the suppository base under the influence of either gravity or ambulation before it can start solubilizing in liquid. There is no requirement for fluid to be present in order for lipophilic melting suppositories to soften and disseminate. The same drug transport seen in dissolving suppositories will take place in melting suppositories as the suppository liquefies under heat.⁷⁶

The patient should reportedly be lying on their left lateral side with their right leg bent while the suppositories are being placed. Prior to usage, the suppositories should be dipped in water to make them easier to insert. If the suppositories are too soft to insert, particularly in warm weather, they should be placed in cold water or the refrigerator for 30 minutes prior to use.⁷⁷

HERBAL SUPPOSITORIES USED IN VARIOUS DIFFERENT DISEASES:

Table 1: Commonly used medicinal plants in Rectal Suppositories formulations with their scientific names, temperaments, used parts, ethno medicinal and approved indications

Scientific name	Temperament	Used part	Ethno medicinal indications	Approved indications
Astragalus fasciculifolius Boiss	Hot and dry	Gum resin	Healing wound	Healing wound¹⁹
Dorema ammoniacum D.Don	Hot and dry	Oleo gum resin	Healing sciatic, joint pains and lumbago, anthelmintic effect	-
Ferula gummosa Boiss	Hot and dry	Gum resin	Anti-hemorrhoids, healing wound, relieving lumbago	Anti-inflammatory effect ²⁰
Zingiber oficinale Roscoe	Hot and dry	Rhizome	Relieving flatulent colic, sciatic and joint pains, anthelmintic and aphrodisiac effect	Relieving rheumatoid arthritis, anti-inflammation, relieving intestinal spasms, laxative and anthelmintic effects, increasing sperm percent and serum total testosterone²¹
Apium graveolense L.	Hot and dry	Seed	Carminative and laxative effects, healing sciatic pains and lumbago	Anti-inflammatory and analgesic effects22
Zingiber zerumbet (L.) smith	Hot and dry	Root	Healing cold pains, aphrodisiac effect	Anti-inflammatory effect and pain-mediated diseases²³
Cyperus longus L.	Hot and dry	Root	Anti-hemorrhoids, aphrodisiac effect	⁸¹
Euphorbia helioscopia L.	Hot and dry	Gum	Anthelmintic effect, relieving colic, sciatic, joint pain and lumbago	Anthelmintic effect²⁴
Cinnamomum camphora L	Cold and dry	Wood	Anti-fever	-
Malva rotundifolia L.	Cold and wet	Aerial parts	Anti-dysentery, laxative effect	-
Trigonella foenum-graec um L.	Hot and dry	Seeds and leaves	Relieving lumbago, anti-ascites, laxative and aphrodisiac effects	Enhancing testosterone level and sexual function ^{25, 26} anti-inflammatory and anti-arthritic effects^{27, 28}
Linum usitatissimum L.	Cold and dry	Seed	Anti-hemorrhoids, relieving sciatic and joint pains	Anti-inflammatory and analgesic effects, anti- diarrhea and anti-constipation²⁹
Ricinus communis L.	Hot and dry	Seed	Laxative effect, relieving colic, lumbago and anti-ascites	Antiulcer and anti-inflammation, healing wound³⁰
Iris pseudoacorus L.	Hot and dry	Rhizomes	Anti-hemorrhoids, relieving sciatic pains, anti-ascites, laxative effect	-
Artemisia absinthium L	Hot and dry	Root	Anthelmintic effect, relieving obstructive colic, anti-hemorrhoids, healing joint pains	Anti-inflammatory effect anti-parasites^{31, 32}
Nigella sativa L.	Hot and dry	Seed	Relieving flatulent colic, anti-hemorrhoids, healing joint pains, anthelmintic effect	Anti-inflammatory, analgesic and anti-parasitic actions³³
Trachyspermu m ammi (L.) Sprague	Hot and dry	Seed	Relieving flatulent colic, anthelminthic and aphrodisiac effects, anti-ascites	Antispasmodic activity, anti-inflammatory, nematicidal and anthelmintic activities3⁴
Aloe vera L.	Hot and dry	Latex	Anthelmintic and laxative effects	Laxative effect35
Cassia fistula L.	Hot and wet	Fruit	Relieving obstructive colic, laxative effect	Laxative effect36
Punica granatum L.	Cold and dry	Flowers	Anti-diarrhea	-
Boswellia sacra Flueck.	Hot and dry	Gum resin	Anti-dysentery, healing wound, anti-hemorrhoids and anti-diarrhea	Analgesic effect37
Quercus spp	Cold and dry	Fruit and Gall	Anti-hemorrhoids, anti-diarrhea	Anti-inflammation38
Terminalia chebula L	Cold and dry	Fruit	Anti-ascites, anti-hemorrhoids, anti-diarrhea	Anti-diarrheal and anti-inflammatory activities39, 40, 41
Terminalia bellerica L.	Cold and dry	Fruit	Anti-diarrhea	Anti-diarrhea42
Phylantus emblica L.	Cold and dry	Fruit	Aphrodisiac effect, anti-hemorrhoids, anti-diarrhea	Anti-diarrhea, anti-dysentery, anti-inflammation43
Althaea of icinalis L.	Cold and wet	Flowers	Anti-fever, relieving obstructive colic, laxative effect	-
Crocus sativus L	Hot and dry	Flowers	Anti-dysentery, relieving obstructive colic, healing wound	Relaxant activity44
Colchicum L	Hot and dry	Root	Relieving flatulent colic, sciatic & joint pain	Anti-arthritic activity45
Ferula asa foetida L.	Hot and dry	Oleo gum resin	Carminative, anthelmintic and aphrodisiac effects, anti-hemorrhoids	Antispasmodic, anthelmintic, anti-ulcerogenic, and anti-inflammatory activities46
Viola odorata L.	Cold and wet	Aerial parts	Anti-fever, relieving obstructive colic	-
Sacharrum of icinarum	Hot and wet	Stem extract	Purgative aphrodisiac effect	71
Citrullus colocynthis (L.) Schrad	Hot and dry	Fruit and seed	Anthelmintic and purgative effects, relieving flatulent colic, sciatic and joint pains, anti-hemorrhoids	Purgative activity and anti-ulcer47
Papaver somniferum L.	Cold and dry	Latex	Anti-dysentery, relieving obstructive colic, anti-diarrhea	Analgesic effect, anti-diarrhea, anti-dysentery^{48, 49, 50}
Myrtus communis L.	Cold and dry	Fruit	Anti-diarrhea, anti-hemorrhoids	Anti-inflammatory, analgesic and anti-parasitic effect51
Commiphora myrrha (Nees) Engl.	Hot and dry	Oleo gum resin	Relieving obstructive colic, anti-dysentery, healing wound	-
Plantago major L.	Cold and dry	Seeds and leaves	Anti hemorrhoids, anti-dysentery and anti-diarrhea	Anti-ulcerogenic, Anti-inflammatory and analgesic activities52
Polygonatum orientale Desf.	Hot and dry	Rhizome	Relieving sciatic and joint pain	-
Commiphora mukul Engl.	Hot and dry	Oleo gum resin	Relieving sciatic and joint pain, carminative effect	Anti‐inflammation53
Ferula persica Willd.	Hot and dry	Gum-resin	Anti-dysentery, relieving flatulent colic, sciatic and joint pain	Anti-inflammation54
Senna alexandrina Mill.	Hot and dry	Leaves and fruit	Relieving obstructive colic, laxative effect	Laxative effect55
Convolvulus scammonia L.	Hot and dry	Oleo gum resin	Relieving flatulent colic and sciatic pain, purgative effect	74
Anacyclus pyrethrum (L.) Lag.	Hot and dry	Roots	Relieving sciatic and joint pain, aphrodisiac effect	Improving male fertility by inducing spermatogenesis56
Acacia nilotica (L.) Delile	Hot and dry	Gum	Anti-dysentery, healing wound, anti-hemorrhoids, anti-diarrhea	Wound dressing material for bleeding and profusely exuding wounds52

SOME OTHER COMMON DISEASES TREATED BY SUPPOSITORIES:

1. VAGINITIS DUE TO SACCHAROMYCES CEREVISIAE:

Though these infections are fairly uncommon, vulvovaginitis brought on by Saccharomyces cerevisiae may benefit from the use of boric acid vaginal suppositories. A report of a 30-year-old female with recurrent vaginitis that had occurred five months earlier and from which C. glabrata was isolated. Clotrimazole, terconazole, ketoconazole, intravenous amphotericin B, or oral flucytosine did not help the patient. A 600 mg daily dose of vaginal boric acid suppositories eventually led to a clinical and mycological cure.⁵⁷The patient, who was still getting boric acid, was discovered to be S. cerevisiae colonized and had developed frank vulvovaginitis. This condition was treated by increasing the dosage of boric acid to 600 mg twice day. After six months of boric acid maintenance medication, the patient was still symptom-free. With the help of boric acid suppositories, relapse after stopping treatment was completely eliminated. The authors also assessed the susceptibility of 20 clinical isolates of S. cerevisiae, and they discovered that extended treatment with 600 mg/day of boric acid was linked to clinical and mycologic resolution in four episodes; however mycologic clearance required protracted treatment.

2. RESISTANT CANDIDAL VAGINITIS:

There have been a number of examples where boric acid has been used to treat azole-refractory candidal vaginitis. After nine months of daily treatment with 100 mg of fluconazole, a 32-year-old woman with severe acquired immunodeficiency syndrome (AIDS) and a CD4 level of 10/mm3 developed vulvovaginal candidiasis and thrush. This case was described by Shinohara and Tasker. Fluconazole-resistant strains of C. krusei and C. glabrata were detected in cultures.⁵⁸Itraconazole failed to control the patient's symptoms, nystatin only marginally improved them, and the patient found the gentian violet topical solution to be disappointing in terms of appearance. Treatment with 5% boric acid in lanolin vaginal suppositories and 600 mg twice daily of boric acid relieved symptoms and was well tolerated. The serum did not contain any boric acid. Three relapses occurred five months after the patient's initial therapy; these were treated with two- to three-day treatments of boric acid.

3. POST- CESAREAN SECTION PAIN:

Opioids have historically been viewed as being replaced by alternative analgesics due to the vast range of negative effects and dependence they are associated with. NSAIDs prevent the cyclooxygenase enzyme, which catalyses the conversion of arachidonic acid to prostaglandin, from doing its job.^{59, 60}The peripheral nervous system may experience less pain by producing fewer of these substances.

Abdollahi et al. found no difference in the mean pain score between the two groups at the first eight hours, but at the second and third eight hours, the feeling of pain was statistically lower in the diclofenac group. Pethidine (0.5 mg/kg intrathecal every eight hours) and diclofenac suppository (100 mg every eight hours) were compared for pain relief after inguinal herniation surgery.⁵⁹The mean pain scores in the diclofenac group were lower than those in the pethidine group at 10, 18, and 26 hours after surgery, but the reported pain severity had lessened more over time. This difference between the two groups may be brought on by diclofenac's prolonged effects, it’s blocking of pain receptors, and its inhibition of prostaglandin release.

4. ANAL DISORDERS:

Anus is the portion of the gastrointestinal system that travels via the anal sphincters and muscular canal of the pelvis. The body's last opening via which stool exits is this one. The anus is 4–5 cm long in adulthood. Sensitive nerve endings line the lower portion of the anal canal. Under the lining are blood arteries, and in the middle is a great deal of little anal glands.

Suppositories could well be looked as a convenient drug delivery system in patients having ano-rectal symptoms. Some suppositories formulation is described below in the table form for the various ano-rectal pathologies.

Table 2: Suppositories for various ano-rectal pathologies

Bleeding hemorrhoids	astringents, vasoconstriction, protectants, Calciaum dobiselate and Policresulen
Hemorrhoidal thrombosis	Local anesthesics, vasoconstrictions and calcium dobiselate
Assam fissure	Local anesthetics, steroids, protectants, antiseptics, keratolytics and Policresulen
Pruritus ani	Steroids, astringents and protectants
Anal cryptitis and proctitis	Local anesthetics, astringents and antiseptics
Anal rhagades	Keratolytic, antiseptics and policresulen
Post and surgery	Local anesthetics, vasoconstrictions, antiseptics and Calsium dobiselate

5. ULCERATIVE PROCTITIS:

A form of ulcerative colitis called ulcerative proctitis (UP) is characterized by rectal bleeding, tenesmus, irregular bowel movements, and rectal pain. Ulcerative colitis (UC) is a chronic inflammatory disease that results in long-lasting inflammation and ulcers of varying sizes in the colon.⁶¹ In Ulcerative proctitis, the rectum is the only area of inflammation. In Asia and Australia, respectively 37% and 32% of those who have Ulcerative Colitis are actually suffering with Ulcerative Proctitis.⁶²Mesalamine rectal therapy in the form of suppositories or enemas has shown to have high concentrations of the active ingredient at the site of inflammation and limited systemic absorption, ⁶³ making it typically the first option for UP suggested in various international guidelines.^64-66The active ingredient in sulfasalazine is mesalamine (5-aminosalicylic acid), which has numerous anti-inflammatory actions, including the suppression of cyclooxygenase, lipoxygenase, B-cells, and several important inflammatory cytokines.⁶⁷

6. PARKINSON’S DISEASE:

Parkinson's disease is a slowly developing, chronic neurodegenerative condition that primarily affects the motor system (bradykinesia, stiffness, rest tremor, and postural problems). Along with late-onset motor symptoms (such postural instability and falls, freezing of gait, speech and swallowing difficulties), it is also linked to a variety of non-motor symptoms.^{68, 78}

For the best seizure control during both the acute and long-term therapy of Parkinson's disease, the drug's therapeutic concentration must be maintained.⁷⁹ When chronic medication delivery is necessary but oral access to the medication is restricted or the IV formulation of the medication is incompatible, alternate drug dosing routes are needed. Rectal injection of anti-Parkinson drugs is crucial since it partially avoids first pass metabolism. Since many years ago, children's recurrent or protracted seizures have been treated with diazepam by rectal route in the form of solution and gel preparation. When injected rectally, diazepam solution absorbs completely and quickly, reaching peak plasma concentration in 5 to 15 minutes.^69,80

7. FUNGAL INFECTION IN CERVICAL CANCER PATIENTS:

Cervical cancer is one of the most common cancers, and among women, it is also the one that causes the second-highest cancer mortality rate. Patients with cancer are more likely to develop and die from fungal infections than from other illnesses. The likelihood that a patient will get a fungal infection can be decreased by prescribing antifungal drugs.⁷⁰

Curcumin, the herbal drug that was selected for the current study, is a well-known contender with antifungal and anticancer effects. Curcumin has been used extensively in the study of cancer prevention. The newly created curcumin vaginal suppository may be a natural remedy free from side effects that helps cervical cancer patients avoid candidiasis and may also help with cancer treatment.

CONCLUSION:

Suppositories are solid dosage forms which are meant to be administered through body orifices (such the urethra, vagina, ear, nasal and rectal cavity), where they can exert a local or systemic effect after melting, softening, or dissolving.The therapeutic effect of suppositories is determined by the complex interaction between the pharmaceutical contents and the suppository substrate, which has structural-mechanical or rheologic properties. In this article, an analytical review of the variety of contemporary herbal suppository formulation, insertion technique, types, dose characterization, and bases used is carried out, along with a description of their physical and chemical properties, advantages, and disadvantages. This allows one to select an appropriate excipients and the particular drug content in the future in order to develop new medications in the form of herbal suppositories.Suppositories provide patients a choice that is easier to use and less discomforting. In summary, many different analytical methods from wet chemistry to modern instrumental methods can be used for analytical testing of suppositories, after sampling and sample preparation. A complete method development is required to ensure accuracy, precision, and reproducibility. Suppositories are useful as sustained release formulations for long-term treatment of chronic diseases such as essential hypertension, asthma, diabetes, AIDS and anemia. In addition to treating pregnancy-related, chemotherapy-related, allergy-related, and anal problems, it is also administered to unconscious and paediatric patients. Suppositories may be considered a practical drug administration method for patients experiencing ano-rectal symptoms. The dosage form's goal is to guarantee that the medications supplied to its citizens are not only safe and effective but also correctly made and packaged to fulfill the defined quality and targeted product profile during the course of its shelf life.

FUTURE ASPECT:

Herbal suppositories will prove to be extremely helpful in the future for drug dosing without first pass metabolism for the treatment of some novel and serious diseases because they are more stable and cost-effective for administration through recently discovered sites for administration, such as the nose and ear cavities, with a small amount of drug formulation and a rapidly effective dose along the sustainable treatment for disease toxicity and preventive purposes for some untreatable conditions.

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Received on 06.05.2024 Revised on 02.07.2024

Accepted on 14.08.2024 Published on 18.12.2024

Available online on December 21, 2024

Asian J. Pharm. Tech. 2024; 14(4):355-362.

DOI: 10.52711/2231-5713.2024.00057