External consultant CMO expansion of onsite formulation and fill-finish services

¶ … Responsibilities as an external consultant to a contract manufacturing organization (CMO)

Research in the field of medicine has contributed to changes in administration of dosage. Initially some administration routes for drugs are considered more convenient than other methods. However this relies and depends on the benefits and shortcomings of the drug administration route. The paper discusses on the possible and the convenient drug administration routes to apply in CMO. The paper also discusses on the methods to improve the physical stability and product chemical in the dosage for CMO

Routes of administration for biological medicinal products

Different routes of administration can be applied for biological medicinal products and generally for contract manufacturing organization (CMO). For instance, enteral, parenteral, and transdermal are the common broad routes of medicinal administration.

Hypodermoclysis administration route

Hypodermoclysis administration route is whereby the dosage is in fluid form and can be referred to as subcutaneous infusion or interstitial infusion. In this case, the dosage is normally in form of glucose or saline solution.

Advantages of Hypodermoclysis

Hypodermoclysis supports or allows for increased rate of drug intake when compared to intravenous infusion. Additionally, this method is cheap and effective. Hypodermoclysis also requires minimal supervision and can even be administered by non-medical personnel. This method is also considered safe since it does not pose serious complications and it is the most effective for the elderly.

Disadvantages of Hypodermoclysis

The major disadvantage of Hypodermoclysis route of drug administration is that it only supports or allows a capacity of 1ml per minute. In essence, it does not support administration of high volumes of dosage.

Transdermal route of administration

This entails the application of the dosage or drug directly to the skin surface and includes the administration of dosage to mucus membrane including lungs, nose, eyes, colon, vagina, and ears. The dose which is administered through this method includes gels, cream, transdermal patches, ointments, and suspensions (Neidle, 2008, p.133).

Advantages of the transdermal

The transdermal route of administration of doses results to less or no side effects. In addition, inhalation sprays through the nose can help in administering doses for curing systemic or local effects since absorption of the drug takes place through the skin (Troy, 2005, p.939). The other advantage is that this route of administration ensures that the blood vessels are stable. The transdermal route of administration also ensures that the first pass metabolism is avoided. An additional advantage of using the transdermal route of administration is that it ensures secure drug level into the system.

Disadvantages of transdermal route

There are cases of local therapeutic problems or effects once this method is used. The other disadvantage is that the dosage is not well absorbed in the lower or deeper skin layer or the mucous membrane. For the case of transdermal, the drug is required to be potent and failure of this might lead to the patch becoming too large.

Enteral

Enteral route of medicine cover a diversity of methods including oral, sublingual, buccal and rectal.

Oral route

Oral administration of medicine entails applying transdermally in the mouth and swallowing for absorption through the gastrointestinal track to system circulation (Kasapis, Norton, & Ubbink, 2009, p.603). Common forms of dose which can be administered using the oral route include liquids, tablets, capsules, syrup, solution, suspension, and elixirs.

Advantages of oral administration

The CMO can apply the oral route in administering medicine following its advantages as identified. Oral administration is convenient since it is pain free, self-administered, and easy when taking. The other advantage of oral administration is that absorption occurs along the entire GI tract length. In addition, oral administration is cheap compared to the other parental routes.

Disadvantages of oral administration route

CMO should also understand that oral administration route is bound to some shortcomings. In some cases, oral is considered inefficient since not all the drug is absorbed. Oral also has the disadvantage of effect of first pass which implies that drugs administered using this route pass through the portal vein to the liver. The oral administration route also leads to irritation of the gastric mucosa which eventually results to vomiting and nausea (Neidle, 2008, p.133). More often, the oral route is not recommended for emergency cases since it responds slowly and can not apply in cases where the patient is unconscious. Since some drugs have unpleasant taste, this administration route might be a challenge especially to young children. Digestive and gastric juices contribute towards destruction of the drugs.

Limb perfusion

Limb perfusion entails a medical technique which is generally applied in delivering anti-cancer dosage through the arm or leg. Blood flow is first stopped for a short duration using a tourniquet and the dosage is the administered directly to the blood in the limb.

Advantages of limb perfusion

Limb perfusion is the most effective method of drug administration in treating cancer. Additionally, limb perfusion ensures quick absorption of the administered drug (Limited, 2003, p.383). This method also ensures administration of high dosage compared to other methods.

Disadvantage of Limb perfusion

Initially, just like the other methods of drug administration, limb perfusion is associated with elevated risk which comprise of persisting impairment concerning the treated limb (Mahdi & Abolfazl, 2011, p.213). Another disadvantage of this method is that it is utilized in treating cancer but it can merely apply in treating other ailments.

The rectal route

This is whereby the drug is administered through enema or subsitory method. Some examples of rectal dosage include theophylline, chlorpromazine, and aspirin (Adikwu, & Esimone, 2009, p.1).

Advantages of rectal route

The rectal route administration of dosage can be used for cases involving children, it is also known to cause little, and in other cases no first pass effect (Adikwu, & Esimone, 2009, p.1). The other advantage of this method of administering dosage is that it works effectively for voting cases and lastly, this method is known to enhance high and rapid concentration.

Disadvantages of rectal route

Rectal route administration of dosage support erratic and slow absorptions. In addition, rectal mucosa suffers from inflammation and irritation once the rectal route s applied in administering dosage. This method of administering dosage is also not convenient.

Systemic-parenteral route

This is infusion or injection by the use of a catheter or a needle inserted into the body. In this case, the alimentary canal is the one used as the route of administration (Gillespie et al., 2010, p.830). Different types of injectables are used in this case including intramuscular, intravenous, subcutaneous, intra-arterial, intrathecal, intra-articular, and intradermal.

Advantages of parenteral route of administration

The route is convenient for cases where drugs administered orally are destroyed by secretions such as antibiotics and insulin. The route triggers a physiological reaction which may be useful in patient situations, for example, shock or heart attack. The method is convenient because it allows passage of medicines through injections, especially for stubborn patients. Parenteral route allows a patient to feed, in cases where the patient is unable to feed via the mouth.

Disadvantages of parenteral route

The paranteral consumes more time than other routes and also requires skilled persons. While using the route, conformance with various aseptic procedures is required. In addition, the patient cannot avoid the pain at the period of administration. The route is associated with physiological effects which are complex to reverse. The specifications for manufacturing and packaging for parenteral dosage states are expensive compared to other forms.

Advantages of intramuscular route

This administration route ensures uniform absorption. It also facilitates rapid onset of action (Gillespie et al., 2010, p.830). The other advantage of intravascular route is that it can be applied in cases of mild irritants and ensures that first pass is avoided. In addition, the intramuscular route of administration also ensures that gastric factors are avoided.

Disadvantages of intramuscular route

The drug dosage which can be administered using this method if limited to 10ml. local abscess and pain are also experienced when this administration route is applied. The other disadvantage of using this administration route is that it may lead to infection and nerve damage.

Advantages of Intravenous route

This administration route ensures that the desired concentration of blood is achieved. Moreover, it ensures administration of large quantity dosage and can useful in situations of diarrhea and vomiting (Staphylococcus aureus vaccine conjugate -- Nabi: Nabi-StaphVAX, StaphVAX' 2003, p.383). It is also suitable for emergency cases. Intravenous route ensures avoidance of the first pass and gastric manipulation.

Disadvantages of intravenous route

This administration route contributes towards cellulites and irritation. Moreover, it also poses some dangers of infection, expensive, painful, and less convenient (Neidle, 2008, p.133). The other disadvantage is that this administration route has less space and highly depends on technical assistance. It also leads to repetition in injections which are not always feasible as well as leading to thrombophelebitis.

The selection of the best route for CMO

The factors to consider when selecting the route for drug administration depend on the speed for absorption or drug release and the physical distinctiveness of the medicine. In addition, the patient's condition, concentration of the dosage on particular, and dosage accuracy are other factors which also need to be considered when choosing the most convenient route for dosage administration. Therefore, following the analysis of the provided routes of dosage administration, parenteral offers the most convenient choice because of its increased advantages the enteral dose administration route whereas the best method is freeze drying lyophilisation (Adikwu, & Esimone, 2009, p.1). This is to the fact that the parenteral routes support high volume or quantities of dosage and it as a higher response to the system following the part which is suffering.

Common methods used to enhance product stability (formulation and dosage form)

The following are the main available methods used to enhance product stability (formulation and dosage form).

Tablet Dosage Formulation method

This is the most common method of formulation. While using this particular method, it is advisable to start the drug in very fine powder and then continue to press it into a single dosage unit (Arcangelo & Peterson, 2005, p. 45). The following are the recommendable ingredients to use while employing the tablet formulation dosage method.

i. Drug- the drug to use may be poorly soluble or hydrophobic

ii. Lubricant -- the lubricant should be quite hydrophobic.

iii. Granulating agent- the importance of using this kind of agent is to stick the ingredients together.

iv. Filler-this is supposed to be water soluble

v. Wetting agent -- the main purpose of using the water agent is to assist in the penetration of water into the tablet.

vi. Disintegration agent-This is particularly used to help break the tablet apart.

One of the most important issues to note while employing the use of this method is that coated tablets are always usually used with the aim of masking an unpleasant taste. They are also used to protect the tablet ingredients during the storage process. They may also be used with the aim of improving the tablets appearance.

Sustained Release Dosage Formulation

This formulation method tends to improve the drug's both shelf-life and therapeutic half-life in the patient's body. The method tends to create a steady profile hence making the drug available to the patient over an extended period of time after ingestion. The main advantages of using this particular method include uniform release of the drug while in the patient's body (Qiu, Chen & Zhang, 2009, p. 515). The other advantage is the decline in the number of intake. Moreover, there is better patient compliance and reduced side effects after taking the drug. There are a number of methods techniques used when employing the use of this particular technique. Example of these techniques includes:

i. Compression

ii. Capsule filling iii. Melt granulation

iv. Spray cooling

Capsule Dosage Formulation Method

This method entails ensuring that the capsule hard gelatin shell disrupts rapidly. The gelatin shell should also allow the contents of the dosage to mix accordingly with the G-I tract contents. On this case, it is advisable to note that the capsule contents should not be subjected to high compression forces. This is because such forces may contribute to a higher extent in reducing the recommended and effective surface area. The other significant issue to note is that if a drug is hydrophobic, it is always advisable to employ the use of a dispersing agent to the capsule formulation. The significant important of such a diluents is to disperse the powder, minimize aggregation and maximize its surface area (Podczeck & Jones, 2004, p. 226). In some cases, most of the tightly packed capsules tend to have a reduced dissolution. They also tend to have a reduced bioavailability.